This document summarizes the potential for using plants to produce biopharmaceutical proteins through genetic engineering. Modern biotechnology has led to interest in producing therapeutic proteins in plants, which can be done at large scale in a cost-effective manner. The document discusses considerations for the gene expression system and type of plant to use to optimize protein production. Safety and regulatory issues must also be addressed before commercial production of plant-made pharmaceuticals.
This document provides an overview of ethnopharmacology, including definitions of related terms, areas of research, objectives and strategies. Some key points:
- Ethnopharmacology is the scientific study of materials used by cultures as medicines. It aims to document traditional knowledge and validate treatments.
- Major areas of herbal medicine research include Ayurveda, Traditional Chinese Medicine, European and indigenous systems.
- The objectives are to investigate traditional remedies, identify active compounds, and conduct pharmacological studies.
- Strategies for screening plants include literature reviews, selecting candidates, proper collection and processing, and drug screening procedures.
This document discusses ethnopharmacology, which is the scientific study of materials used as medicines by different cultural groups. It notes that ethnopharmacology is a branch of ethnobotany and involves multiple disciplines. The document outlines the historical development of ethnopharmacology and the process of drug discovery using its approach. This includes obtaining information from sources, scientific investigation through extraction, activity testing, and chemical examination. It also discusses some problems and questions regarding ethnopharmacology, such as reliability of information and intellectual property issues.
The document discusses zoopharmacognosy, which is the animal use of plant drugs for self-medication. It provides several examples of non-human primates using medicinal plants, including chimpanzees consuming Aspilia mossambicensis leaves which contain thiarubrine A with anti-parasitic properties. It also describes capuchin monkeys engaging in fur-rubbing behavior with volatile oil-containing plants, and chimpanzees consuming various plants like Ficus exasperata containing compounds like 5-methoxypsoralen that are toxic to parasites. The document outlines similarities between human and primate self-medication and highlights challenges in distinguishing nutrition from medication in animal plant use.
This document discusses the medicinal uses of fungi. It begins with an introduction about how fungi play significant roles in human life as both helpful and harmful organisms. Several fungi, such as Claviceps purpurea and Saccharomyces cerevisiae, have been used for thousands of years to treat various diseases and disorders due to their medicinal properties. Fungi are also used in the production and transformation of important steroids. Additionally, some fungi produce important antibiotics, such as penicillin from Penicillium chrysogenum, and antifungal antibiotics. Other medicinal uses of fungi discussed are their role in vitamin production, production of statins, taxol for cancer treatment, and traditional Chinese medicines like O
The document summarizes research on traditional Maya medicine in Belize. It describes the Q'eqchi' Maya people and their traditional healers who provide primary healthcare using plants. The researchers collaborated with the Kekchi Maya Healer's Association to study various medicinal plants. Their research validated several traditional uses, finding that plants used for epilepsy, anxiety, and inflammation showed pharmacological activities related to their traditional indications. This involved quantitative ethnobotanical studies, laboratory testing of plant extracts, and correlations between traditional use and biological activity. The research aimed to preserve traditional knowledge while scientifically investigating medicinal plants.
BIOTECHNOLOGY
AND ITS APPLICATION TO VETERINARY SCIENCE
Carlos G. Borroto
Deputy Director, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba1
A questionnaire was sent to the 29 Member Countries of the OIE Regional Commission
for the Americas and information and comments were received from the Delegates of 21 Member
Countries. The questionnaire covered aspects relating to the application of biotechnology to
animal health, especially prevention-related issues, including: the development and production of
medicinal products and vaccines; the use of metabolic modifiers, probiotics and prebiotics;
advanced veterinary diagnostic methods; immunocastration and other applications. The
questionnaire also covered the aspects of regulations and public perceptions.
The report analyses the situation in the countries of the region in relation to the state of the art in
these technologies worldwide, revealing that modern biotechnology-based technologies offer huge
potential for the production of vaccines, medicinal products and other veterinary products.
The development and use of these technologies is concentrated in a few countries of the region,
while in others they are still not in widespread use. This creates the need to publicise and provide
training in these technologies, for which suitable development conditions exist in a number of
countries in the region. It is also necessary to foster the establishment of a comprehensive and
effective regulatory framework for the safe use of these technologies from the dual standpoint of
biosafety and of the regulations established in the veterinary register. All the countries of the
region consider that it is important for the OIE to issue additional standards for the production of
veterinary products using modern biotechnology.
Medicinal fungi have been used in traditional medicine for centuries. Modern discovery began in 1928 with penicillin. Fungi produce metabolites that can treat cancer, bacterial infections, high cholesterol, fungal infections, immunosuppression, malaria, diabetes, psychotropic effects, and provide vitamins. They synthesize antibiotics, anti-cancer compounds, statins, antifungals, and more. Medicinal fungi remain an important source of new drugs and treatments.
Pharmaceutical biotechnology is the application of biotechnology principles to develop drugs. It aims to design drugs tailored to an individual's genetics for maximum therapeutic effect. Key applications include recombinant DNA vaccines, drugs, and proteins. Advantages include pharmacogenomics to customize medicine based on genetics. Recombinant DNA and monoclonal antibodies also provide opportunities for new drug development and delivery approaches. Common biotechnology products are antibodies, proteins, and recombinant DNA products. Therapeutic uses include detecting and treating genetic diseases, cancer, AIDS, and autoimmune diseases.
This document provides an overview of ethnopharmacology, including definitions of related terms, areas of research, objectives and strategies. Some key points:
- Ethnopharmacology is the scientific study of materials used by cultures as medicines. It aims to document traditional knowledge and validate treatments.
- Major areas of herbal medicine research include Ayurveda, Traditional Chinese Medicine, European and indigenous systems.
- The objectives are to investigate traditional remedies, identify active compounds, and conduct pharmacological studies.
- Strategies for screening plants include literature reviews, selecting candidates, proper collection and processing, and drug screening procedures.
This document discusses ethnopharmacology, which is the scientific study of materials used as medicines by different cultural groups. It notes that ethnopharmacology is a branch of ethnobotany and involves multiple disciplines. The document outlines the historical development of ethnopharmacology and the process of drug discovery using its approach. This includes obtaining information from sources, scientific investigation through extraction, activity testing, and chemical examination. It also discusses some problems and questions regarding ethnopharmacology, such as reliability of information and intellectual property issues.
The document discusses zoopharmacognosy, which is the animal use of plant drugs for self-medication. It provides several examples of non-human primates using medicinal plants, including chimpanzees consuming Aspilia mossambicensis leaves which contain thiarubrine A with anti-parasitic properties. It also describes capuchin monkeys engaging in fur-rubbing behavior with volatile oil-containing plants, and chimpanzees consuming various plants like Ficus exasperata containing compounds like 5-methoxypsoralen that are toxic to parasites. The document outlines similarities between human and primate self-medication and highlights challenges in distinguishing nutrition from medication in animal plant use.
This document discusses the medicinal uses of fungi. It begins with an introduction about how fungi play significant roles in human life as both helpful and harmful organisms. Several fungi, such as Claviceps purpurea and Saccharomyces cerevisiae, have been used for thousands of years to treat various diseases and disorders due to their medicinal properties. Fungi are also used in the production and transformation of important steroids. Additionally, some fungi produce important antibiotics, such as penicillin from Penicillium chrysogenum, and antifungal antibiotics. Other medicinal uses of fungi discussed are their role in vitamin production, production of statins, taxol for cancer treatment, and traditional Chinese medicines like O
The document summarizes research on traditional Maya medicine in Belize. It describes the Q'eqchi' Maya people and their traditional healers who provide primary healthcare using plants. The researchers collaborated with the Kekchi Maya Healer's Association to study various medicinal plants. Their research validated several traditional uses, finding that plants used for epilepsy, anxiety, and inflammation showed pharmacological activities related to their traditional indications. This involved quantitative ethnobotanical studies, laboratory testing of plant extracts, and correlations between traditional use and biological activity. The research aimed to preserve traditional knowledge while scientifically investigating medicinal plants.
BIOTECHNOLOGY
AND ITS APPLICATION TO VETERINARY SCIENCE
Carlos G. Borroto
Deputy Director, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba1
A questionnaire was sent to the 29 Member Countries of the OIE Regional Commission
for the Americas and information and comments were received from the Delegates of 21 Member
Countries. The questionnaire covered aspects relating to the application of biotechnology to
animal health, especially prevention-related issues, including: the development and production of
medicinal products and vaccines; the use of metabolic modifiers, probiotics and prebiotics;
advanced veterinary diagnostic methods; immunocastration and other applications. The
questionnaire also covered the aspects of regulations and public perceptions.
The report analyses the situation in the countries of the region in relation to the state of the art in
these technologies worldwide, revealing that modern biotechnology-based technologies offer huge
potential for the production of vaccines, medicinal products and other veterinary products.
The development and use of these technologies is concentrated in a few countries of the region,
while in others they are still not in widespread use. This creates the need to publicise and provide
training in these technologies, for which suitable development conditions exist in a number of
countries in the region. It is also necessary to foster the establishment of a comprehensive and
effective regulatory framework for the safe use of these technologies from the dual standpoint of
biosafety and of the regulations established in the veterinary register. All the countries of the
region consider that it is important for the OIE to issue additional standards for the production of
veterinary products using modern biotechnology.
Medicinal fungi have been used in traditional medicine for centuries. Modern discovery began in 1928 with penicillin. Fungi produce metabolites that can treat cancer, bacterial infections, high cholesterol, fungal infections, immunosuppression, malaria, diabetes, psychotropic effects, and provide vitamins. They synthesize antibiotics, anti-cancer compounds, statins, antifungals, and more. Medicinal fungi remain an important source of new drugs and treatments.
Pharmaceutical biotechnology is the application of biotechnology principles to develop drugs. It aims to design drugs tailored to an individual's genetics for maximum therapeutic effect. Key applications include recombinant DNA vaccines, drugs, and proteins. Advantages include pharmacogenomics to customize medicine based on genetics. Recombinant DNA and monoclonal antibodies also provide opportunities for new drug development and delivery approaches. Common biotechnology products are antibodies, proteins, and recombinant DNA products. Therapeutic uses include detecting and treating genetic diseases, cancer, AIDS, and autoimmune diseases.
1) The document discusses the history of antibiotics from ancient times to modern developments. It describes early uses of molds and fungi to treat infections dating back thousands of years.
2) Alexander Fleming's accidental discovery of penicillin in 1928 is discussed as a major breakthrough, though its potential was not realized until the 1940s with the work of Florey and Chain.
3) The modern production of various classes of antibiotics is summarized, including natural, semisynthetic, and synthetic antibiotics and some of the major classes and examples. The ideal properties of antibiotics and their mechanisms of action are also briefly covered.
This document provides a history of genetics, beginning with Gregor Mendel's work with pea plants in 1866. It describes how Mendel's principles were rediscovered in 1900 and widely accepted by 1925. Geneticists then turned to investigating the physical nature of genes, leading to the identification of DNA as the genetic material in the 1940s-1950s. The document also outlines several branches of modern genetics including cytogenetics, biochemical genetics, physiological genetics, clinical genetics, and radiation genetics. It discusses applications of genetics in areas like agriculture, medicine, biotechnology, and genetically modified foods.
This document provides information about the aesthetic and scientific value of insects. It discusses how butterflies are often seen as beautiful symbols of freedom and peace in art. It then provides taxonomic classifications and descriptions of various butterfly species. The document also discusses silk production from silkworms and how silk is used medically. It notes several scientific uses of insects, honey, and other substances produced by insects, including for wound treatment, sleep aid, and pain relief. Insects like maggots, beetles, and ants are discussed for their potential medical applications. The document closes by describing how some insect species can serve as bioindicators of environmental health.
The document discusses the antimicrobial properties of Acacia nilotica plant extracts. It summarizes that phytochemical analysis confirmed the presence of various phytochemicals in A. nilotica like saponins, terpenoids, steroids, anthocyanins, coumarins and tannins. Extracts of A. nilotica showed potential antimicrobial activity against both gram-positive and gram-negative bacteria as well as the fungus Aspergillus niger, suggesting its extracts possess antimicrobial properties and could lead to isolation of novel compounds with healthcare applications.
This document discusses the field of ethnopharmacology, which is the scientific study of medicinal substances used by different cultural groups. It provides examples of many plants and the indigenous medicinal uses of those plants, including yew, coca, willow, opium poppy, and ginseng. It also describes how some modern pharmaceuticals were developed from studying ethnopharmacological substances, such as aspirin from willow bark, quinine from cinchona, and taxol from yew trees.
Toxins produced by bacteria can be divided into two main categories: exotoxins and endotoxins. Exotoxins are soluble proteins released by bacteria into the surroundings that can travel through the body and target specific cells. Endotoxins are components of the outer cell membrane of gram-negative bacteria that are released when the bacteria lyse and cause fever, blood clots, and tissue damage by stimulating an immune response. Both exotoxins and endotoxins can have serious pathological effects but exotoxins have also found medical uses in vaccines and targeted cancer therapies.
Functional Overview of the Biotechnology IndustrythinkBiotech
Comprehensive introductory presentation on the business of biotechnology describing legal, commercial, scientific, and regulatory foundations; used in biotech MBA programs.
1) Pharmacognosy is the study of drugs from natural sources, especially medicinal plants. It draws from fields like botany, chemistry, and pharmacology.
2) Many important drugs were originally derived from plants, including morphine, quinine, taxol, and physostigmine. Extracting and isolating the active compounds from plants was an important early step in drug development.
3) While many plant-derived drugs can now be synthesized, plants remain an important source of new drug leads and templates for designing novel pharmaceuticals due to their vast chemical diversity and potential for novel structures. Extensive further screening of plants is still needed.
Atlanta Botanical Garden Science Cafe: Medicines from Nature - 2014Cassandra Quave
This document provides an overview of Dr. Cassandra Quave's work in ethnobotany and ethnopharmacology. It discusses her early adventures studying medicinal plants used by indigenous groups in the Amazon rainforest and Southern Italy. It then describes her ethnobotanical research methods which include interviews, plant collection and extraction. Several case studies are presented on plants from Southern Italy and Albania that were found to have anti-biofilm and antimicrobial properties. The document emphasizes the multidisciplinary nature of ethnobotany and the importance of collaboration in furthering the field's contributions to drug discovery and local health.
The Qore Defense Organic Mushroom Complex combines six medicinal mushroom varieties known to support immune system activity. Each mushroom has a specific role and they work synergistically for outstanding immune support. The mushrooms are organically grown and include Reishi, Cordyceps, Coriolus, Zhu Ling, Maitake, and Shiitake. The product is designed to support healthy immune function, activate natural killer cells, help maintain health during seasonal changes, and increase energy.
The document summarizes a study on the antibacterial properties of four medicinal plants: Ocimum sanctum, Cinnamomum zeylanicum, Xanthoxylum armatum, and Origanum majorana. Ethanol extracts of the plants were tested against 10 bacterial strains using agar well diffusion and broth microdilution methods. The extracts showed greater activity against gram-positive than gram-negative bacteria. Xanthoxylum armatum demonstrated the largest zone of inhibition against Bacillus subtilis. Origanum majorana exhibited the strongest overall antibacterial activity. The minimum bactericidal concentration was lowest for Origanum majorana at 2.5 mg/ml. The results suggest these
Neem is a village dispensary free and freely available all over India, with a great fight India could win back its patient from an US company.
If anyone asks me choose a single herb for curing the multiple ailment of mankind NEEM will be first herb of my choice
Prof. Dr Sanjeev Sood
PHARMACEUTICAL BIOTECHNOLOGY BY PHARM.ISA HASSAN ABUBAKARISAHASSANABUBAKAR68
PHARMACEUTICALS BIOTECHNOLOGY IS A BRANCH OF SCIENCE THAT INVOLVES THE USE OF RECOMBINANT DNA FOR THE EFFECTIVE MANUFACTURE OF SOME EFFECTIVE DRUGS OR MEDICINE,EXAMPLE LIKE RECOMBINANT DNA VACCINE,RECOMBINANT DNA DRUGS,RECOMBINANT DNA ENZYMES,RECOMBINANT DNA INSULIN,RECOMBINANT DNA YEAST E.T.C. NOWADAYS PHARMACEUTICAL INDUSTRIES USES THIS RECOMBINANT DNA IN THE PRODUCTION OF VARIOUS CATEGORIES OF MEDICINES.
PRESENTED BY ISA HASSAN ABUBAKAR FROM NIGERIA
1) Andrographis paniculata is a traditional medicinal herb that contains various immunomodulatory compounds like andrographolide.
2) The study aims to evaluate the immunomodulatory effects of A. paniculata extracts on mice.
3) The methodology involves collecting and extracting A. paniculata, testing for toxicity, and examining pharmacological effects on immune markers in mice serum and organs. Statistical analysis will be conducted to analyze the effects.
(1) The document discusses endophytes, which are microorganisms that live within plant tissues without causing harm. (2) It describes the types of endophytes including bacteria, fungi, algae, and oomycetes and provides examples of each. (3) Endophytes interact with their host plants in mutualistic ways such as enhancing resistance to pathogens, producing compounds that inhibit other microbes, and promoting plant growth.
Entomopathogens such as bacteria, fungi, viruses and nematodes have potential as biological control agents against insect pests. They are safe for the environment and non-target organisms as their toxins are often specific to certain insect species. Entomopathogens can help manage pest resistance, provide alternatives to chemical pesticides, and are seen as promising for the future of commercial biopesticides. However, their use also faces constraints like short shelf life, lack of awareness, and dependence on proper application timing and techniques.
New Dietary Supplements from Medicinal Mushrooms: Dr Myko San–A Registration ...Jolene1981
ABSTRACT: In December 2010 the Ministry of Health and Social Welfare of the Republic of Croatia registered
tablet preparations AGARIKON.1 and MYKOPROTECT.1, developed by Dr Myko San—Health From Mushrooms
Co., as dietary supplements. This may be the first time for a European manufacturer to successfully register its own
medicinal mushroom products in a European country. As a product with a very broad spectrum of action, officially
described as a preparation for immunity strengthening and general health improvement, AGARIKON.1 is a result of
20 years of research and practice, and is based on the formulation that has achieved the best tumor growth inhibition
rates—above 90% on tumor cell lines of mouse squamous cell carcinoma and fibrosarcoma.
Since the usage of massive dosages of proprietary blended liquid mushroom extracts in patients with breast,
colorectal, lung, and other cancers significantly improved their survival rates, alleviated side effects of standard
oncological therapies, improved their quality of life, and resulted in life prolongation—the very idea is that scientifically
verified medicinal mushroom products can be used as powerful biological weapons to fight human malignancies. If
progressive modern medicine were redefined in a more effective and humane way, cancer mycotherapy should be a
part of a broad concept of biological prevention and therapy of cancer. Also, with a very broad spectrum of action,
generally formulated as “to strengthen immunity,” MYKOPROTECT.1 is intended as an important element in the
prevention and fighting of serious viral infections, whether they are caused by well-known viruses (hepatitis, HIV,
etc.) or newly emerging ones.
This document provides an overview of neem and its use as a botanical pesticide. It discusses the history of research on neem and its global recognition. Neem contains over 100 active components including azadirachtin, which has been found to be the most important bioactive component. All parts of the neem tree can be used as a pesticide but seeds are most effective. Neem is an effective, ecofriendly, and economical alternative to chemical pesticides for controlling many insect pests, mites, nematodes, and fungal/bacterial diseases. It acts through multiple modes of action including repellency, antifeedancy, growth regulation, ovicide effects, and more. The document
Introduction, history, scope and present status of Pharmacognosy.pptxGayatriPatra14
Pharmacognosy is the systematic study of drugs from natural sources like plants, animals, and minerals. It involves studying the name, habitat, properties, constituents, uses, and adulterants of natural drugs. Pharmacognosy provides knowledge about biologically active compounds in herbal medicines and their interactions and safety. Recent research has led to isolation of novel compounds from marine organisms and microbes with biological activities, furthering drug discovery efforts. Pharmacognosy plays an important role in connecting various sciences like botany, chemistry, pharmacology and different medical systems.
Sources of crude drug, classification, organized and unorganized drugs.Megha Shah
Organized and unorganized drugs are classified based on whether they are direct parts of plants or animals (organized) or derived through extraction or processing (unorganized). Organized drugs include plant parts like leaves, roots, fruits, and flowers. Unorganized drugs are prepared from plants through incision, drying, or extraction and do not contain cellular tissues, like latex, gums, resins, and plant exudates. Crude drugs can also come from animal sources like hormones and enzymes, as well as microbial, mineral, marine, plant tissue culture, semisynthetic, and recombinant DNA sources.
Complementary and alternative medicine pptSuny Bisshojit
This document discusses medicinal plants and their use as traditional medicines. It notes that medicinal plants have properties similar to conventional drugs and have been used for thousands of years. Some key points made include that 80% of the world's population uses plants as their primary medicine source, and many modern drugs were developed from plant-based compounds, including aspirin, opium, and quinine. The document also provides examples of plants commonly used in traditional medicines from different regions and their therapeutic effects.
1) The document discusses the history of antibiotics from ancient times to modern developments. It describes early uses of molds and fungi to treat infections dating back thousands of years.
2) Alexander Fleming's accidental discovery of penicillin in 1928 is discussed as a major breakthrough, though its potential was not realized until the 1940s with the work of Florey and Chain.
3) The modern production of various classes of antibiotics is summarized, including natural, semisynthetic, and synthetic antibiotics and some of the major classes and examples. The ideal properties of antibiotics and their mechanisms of action are also briefly covered.
This document provides a history of genetics, beginning with Gregor Mendel's work with pea plants in 1866. It describes how Mendel's principles were rediscovered in 1900 and widely accepted by 1925. Geneticists then turned to investigating the physical nature of genes, leading to the identification of DNA as the genetic material in the 1940s-1950s. The document also outlines several branches of modern genetics including cytogenetics, biochemical genetics, physiological genetics, clinical genetics, and radiation genetics. It discusses applications of genetics in areas like agriculture, medicine, biotechnology, and genetically modified foods.
This document provides information about the aesthetic and scientific value of insects. It discusses how butterflies are often seen as beautiful symbols of freedom and peace in art. It then provides taxonomic classifications and descriptions of various butterfly species. The document also discusses silk production from silkworms and how silk is used medically. It notes several scientific uses of insects, honey, and other substances produced by insects, including for wound treatment, sleep aid, and pain relief. Insects like maggots, beetles, and ants are discussed for their potential medical applications. The document closes by describing how some insect species can serve as bioindicators of environmental health.
The document discusses the antimicrobial properties of Acacia nilotica plant extracts. It summarizes that phytochemical analysis confirmed the presence of various phytochemicals in A. nilotica like saponins, terpenoids, steroids, anthocyanins, coumarins and tannins. Extracts of A. nilotica showed potential antimicrobial activity against both gram-positive and gram-negative bacteria as well as the fungus Aspergillus niger, suggesting its extracts possess antimicrobial properties and could lead to isolation of novel compounds with healthcare applications.
This document discusses the field of ethnopharmacology, which is the scientific study of medicinal substances used by different cultural groups. It provides examples of many plants and the indigenous medicinal uses of those plants, including yew, coca, willow, opium poppy, and ginseng. It also describes how some modern pharmaceuticals were developed from studying ethnopharmacological substances, such as aspirin from willow bark, quinine from cinchona, and taxol from yew trees.
Toxins produced by bacteria can be divided into two main categories: exotoxins and endotoxins. Exotoxins are soluble proteins released by bacteria into the surroundings that can travel through the body and target specific cells. Endotoxins are components of the outer cell membrane of gram-negative bacteria that are released when the bacteria lyse and cause fever, blood clots, and tissue damage by stimulating an immune response. Both exotoxins and endotoxins can have serious pathological effects but exotoxins have also found medical uses in vaccines and targeted cancer therapies.
Functional Overview of the Biotechnology IndustrythinkBiotech
Comprehensive introductory presentation on the business of biotechnology describing legal, commercial, scientific, and regulatory foundations; used in biotech MBA programs.
1) Pharmacognosy is the study of drugs from natural sources, especially medicinal plants. It draws from fields like botany, chemistry, and pharmacology.
2) Many important drugs were originally derived from plants, including morphine, quinine, taxol, and physostigmine. Extracting and isolating the active compounds from plants was an important early step in drug development.
3) While many plant-derived drugs can now be synthesized, plants remain an important source of new drug leads and templates for designing novel pharmaceuticals due to their vast chemical diversity and potential for novel structures. Extensive further screening of plants is still needed.
Atlanta Botanical Garden Science Cafe: Medicines from Nature - 2014Cassandra Quave
This document provides an overview of Dr. Cassandra Quave's work in ethnobotany and ethnopharmacology. It discusses her early adventures studying medicinal plants used by indigenous groups in the Amazon rainforest and Southern Italy. It then describes her ethnobotanical research methods which include interviews, plant collection and extraction. Several case studies are presented on plants from Southern Italy and Albania that were found to have anti-biofilm and antimicrobial properties. The document emphasizes the multidisciplinary nature of ethnobotany and the importance of collaboration in furthering the field's contributions to drug discovery and local health.
The Qore Defense Organic Mushroom Complex combines six medicinal mushroom varieties known to support immune system activity. Each mushroom has a specific role and they work synergistically for outstanding immune support. The mushrooms are organically grown and include Reishi, Cordyceps, Coriolus, Zhu Ling, Maitake, and Shiitake. The product is designed to support healthy immune function, activate natural killer cells, help maintain health during seasonal changes, and increase energy.
The document summarizes a study on the antibacterial properties of four medicinal plants: Ocimum sanctum, Cinnamomum zeylanicum, Xanthoxylum armatum, and Origanum majorana. Ethanol extracts of the plants were tested against 10 bacterial strains using agar well diffusion and broth microdilution methods. The extracts showed greater activity against gram-positive than gram-negative bacteria. Xanthoxylum armatum demonstrated the largest zone of inhibition against Bacillus subtilis. Origanum majorana exhibited the strongest overall antibacterial activity. The minimum bactericidal concentration was lowest for Origanum majorana at 2.5 mg/ml. The results suggest these
Neem is a village dispensary free and freely available all over India, with a great fight India could win back its patient from an US company.
If anyone asks me choose a single herb for curing the multiple ailment of mankind NEEM will be first herb of my choice
Prof. Dr Sanjeev Sood
PHARMACEUTICAL BIOTECHNOLOGY BY PHARM.ISA HASSAN ABUBAKARISAHASSANABUBAKAR68
PHARMACEUTICALS BIOTECHNOLOGY IS A BRANCH OF SCIENCE THAT INVOLVES THE USE OF RECOMBINANT DNA FOR THE EFFECTIVE MANUFACTURE OF SOME EFFECTIVE DRUGS OR MEDICINE,EXAMPLE LIKE RECOMBINANT DNA VACCINE,RECOMBINANT DNA DRUGS,RECOMBINANT DNA ENZYMES,RECOMBINANT DNA INSULIN,RECOMBINANT DNA YEAST E.T.C. NOWADAYS PHARMACEUTICAL INDUSTRIES USES THIS RECOMBINANT DNA IN THE PRODUCTION OF VARIOUS CATEGORIES OF MEDICINES.
PRESENTED BY ISA HASSAN ABUBAKAR FROM NIGERIA
1) Andrographis paniculata is a traditional medicinal herb that contains various immunomodulatory compounds like andrographolide.
2) The study aims to evaluate the immunomodulatory effects of A. paniculata extracts on mice.
3) The methodology involves collecting and extracting A. paniculata, testing for toxicity, and examining pharmacological effects on immune markers in mice serum and organs. Statistical analysis will be conducted to analyze the effects.
(1) The document discusses endophytes, which are microorganisms that live within plant tissues without causing harm. (2) It describes the types of endophytes including bacteria, fungi, algae, and oomycetes and provides examples of each. (3) Endophytes interact with their host plants in mutualistic ways such as enhancing resistance to pathogens, producing compounds that inhibit other microbes, and promoting plant growth.
Entomopathogens such as bacteria, fungi, viruses and nematodes have potential as biological control agents against insect pests. They are safe for the environment and non-target organisms as their toxins are often specific to certain insect species. Entomopathogens can help manage pest resistance, provide alternatives to chemical pesticides, and are seen as promising for the future of commercial biopesticides. However, their use also faces constraints like short shelf life, lack of awareness, and dependence on proper application timing and techniques.
New Dietary Supplements from Medicinal Mushrooms: Dr Myko San–A Registration ...Jolene1981
ABSTRACT: In December 2010 the Ministry of Health and Social Welfare of the Republic of Croatia registered
tablet preparations AGARIKON.1 and MYKOPROTECT.1, developed by Dr Myko San—Health From Mushrooms
Co., as dietary supplements. This may be the first time for a European manufacturer to successfully register its own
medicinal mushroom products in a European country. As a product with a very broad spectrum of action, officially
described as a preparation for immunity strengthening and general health improvement, AGARIKON.1 is a result of
20 years of research and practice, and is based on the formulation that has achieved the best tumor growth inhibition
rates—above 90% on tumor cell lines of mouse squamous cell carcinoma and fibrosarcoma.
Since the usage of massive dosages of proprietary blended liquid mushroom extracts in patients with breast,
colorectal, lung, and other cancers significantly improved their survival rates, alleviated side effects of standard
oncological therapies, improved their quality of life, and resulted in life prolongation—the very idea is that scientifically
verified medicinal mushroom products can be used as powerful biological weapons to fight human malignancies. If
progressive modern medicine were redefined in a more effective and humane way, cancer mycotherapy should be a
part of a broad concept of biological prevention and therapy of cancer. Also, with a very broad spectrum of action,
generally formulated as “to strengthen immunity,” MYKOPROTECT.1 is intended as an important element in the
prevention and fighting of serious viral infections, whether they are caused by well-known viruses (hepatitis, HIV,
etc.) or newly emerging ones.
This document provides an overview of neem and its use as a botanical pesticide. It discusses the history of research on neem and its global recognition. Neem contains over 100 active components including azadirachtin, which has been found to be the most important bioactive component. All parts of the neem tree can be used as a pesticide but seeds are most effective. Neem is an effective, ecofriendly, and economical alternative to chemical pesticides for controlling many insect pests, mites, nematodes, and fungal/bacterial diseases. It acts through multiple modes of action including repellency, antifeedancy, growth regulation, ovicide effects, and more. The document
Introduction, history, scope and present status of Pharmacognosy.pptxGayatriPatra14
Pharmacognosy is the systematic study of drugs from natural sources like plants, animals, and minerals. It involves studying the name, habitat, properties, constituents, uses, and adulterants of natural drugs. Pharmacognosy provides knowledge about biologically active compounds in herbal medicines and their interactions and safety. Recent research has led to isolation of novel compounds from marine organisms and microbes with biological activities, furthering drug discovery efforts. Pharmacognosy plays an important role in connecting various sciences like botany, chemistry, pharmacology and different medical systems.
Sources of crude drug, classification, organized and unorganized drugs.Megha Shah
Organized and unorganized drugs are classified based on whether they are direct parts of plants or animals (organized) or derived through extraction or processing (unorganized). Organized drugs include plant parts like leaves, roots, fruits, and flowers. Unorganized drugs are prepared from plants through incision, drying, or extraction and do not contain cellular tissues, like latex, gums, resins, and plant exudates. Crude drugs can also come from animal sources like hormones and enzymes, as well as microbial, mineral, marine, plant tissue culture, semisynthetic, and recombinant DNA sources.
Complementary and alternative medicine pptSuny Bisshojit
This document discusses medicinal plants and their use as traditional medicines. It notes that medicinal plants have properties similar to conventional drugs and have been used for thousands of years. Some key points made include that 80% of the world's population uses plants as their primary medicine source, and many modern drugs were developed from plant-based compounds, including aspirin, opium, and quinine. The document also provides examples of plants commonly used in traditional medicines from different regions and their therapeutic effects.
Bpharm 2 y_4s_405t_pharmacognosy & phytochemistry-iNop Pirom
Pharmacognosy is the study of crude drugs from plants, animals, and minerals. Most crude drugs used in medicine are obtained from plants and include parts like leaves, roots, bark, and seeds. Crude drugs may consist of entire plants or animals or their extracts. Organized drugs are direct plant parts containing cellular tissue, while unorganized drugs do not contain tissue and are prepared through processes like drying or extraction. Pharmacognosy studies these natural substances and their chemical constituents for medical uses as well as in cosmetics, textiles, and food industries. The field has broad applications in academia, private industry, and government agencies.
Ethnobotany and ethnopharmacology involve the scientific study of how different ethnic groups use plants for medicinal purposes. The document discusses the impact of ethnobotany on herbal drug evaluation and traditional medicine. It describes how ethnobotany helps identify new plant-based drugs and molecular models through processes like bioassay-guided purification and structure elucidation. Ethnopharmacology plays a key role in evaluating traditionally used herbal medicines and validating their therapeutic effects through controlled clinical studies.
Screening of antimicrobial activity of indian plants such as Andrographis echoids , Mirabilis jalapa & Canna indica.
A polyherbal extract was made using 4 different solvents i.e. Pet Ether, Chloroform, Ethanol & Aqueous and the method of extraction was soxhlation.
Further Preliminary Phytochemical screening was done and found that presence of Flavonoids were more in Ethanolic extract which was responsible for our activity.
Acute oral toxicity studies were done.
Evaluation was done.
For Final conclusion you can check the ppt.
Pharmacognosy is the study of medicinal plants and natural products. The document traces the historical development of pharmacognosy from ancient civilizations like Babylon, Egypt, India, Greece and China. It discusses how modern pharmacognosy emerged in the 20th century due to discoveries like penicillin. The current status and future scope of pharmacognosy is highlighted, including the importance of natural products in drug development and alternative medicine systems like Ayurveda, Unani, Siddha, homeopathy and traditional Chinese medicine.
Introduction of pharmacognosy & Phytochemistry Vishal Bagul
This document provides an introduction to the topic of pharmacognosy. It defines pharmacognosy and traces its history from ancient Greek and Indian medical practitioners. It describes the modern development of pharmacognosy through the application of various biological and analytical techniques. The document outlines the sources of drugs from plants, animals, and marine organisms. It also classifies drugs based on their organization, morphology, chemistry, pharmacology, taxonomy, and other characteristics. Various applications of pharmacognosy in areas like drug development, extraction, and tissue culture are mentioned as well.
This presentation consists of different insects used for medicinal purpose in day-to-day life for curing diseases without any side effects. The craze of use of insects in medical treatments now-a-days increasing and also proved successful for curing many non curable disease and infections in human body. Many synthetic derivatives are also available in markets. This slide show contains insects and their products used for medical purpose.
This document provides an introduction to pharmacognosy, including definitions, history and sources of drugs from natural origins such as plants, animals and marine sources. It discusses the classification of crude drugs based on various parameters as well as the quality control of natural crude drugs through organoleptic, microscopic, physical, chemical and biological evaluation methods. The topics covered include the scope of pharmacognosy, historical developments, sources of drugs from plants, animals and microbes, and the systematic study of crude drugs.
This document discusses the history and development of pharmacognosy, the study of medicinal plants and natural products. It describes how ancient civilizations like Babylonians, Egyptians, Indians and Greeks made early contributions. Key developments included the first herbal by Dioscorides in the 1st century AD and Pen Ts'ao Kang Mu in the 16th century. Modern pharmacognosy emerged in the 1930s-1960s due to discoveries like penicillin. The field has grown with developments in isolation, identification and structure elucidation of active plant constituents. Pharmacognosy also plays a role in precursor synthesis, formulations and cultivation technology. The future of pharmacognosy is promising due to realizations of natural drug
This document provides an overview of the history and scope of pharmacognosy. It discusses how ancient civilizations like Sumerians, Akkadians, Egyptians and authors of antiquity utilized natural products for medicine. It outlines the isolation of pure compounds in the 18th-19th century and contributions of key figures. The document defines terms, outlines the scheme for studying natural drugs, and discusses plant, animal, marine and mineral sources of drugs. It concludes with the broad scope of pharmacognosy in drug discovery, development and traditional medicine.
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
This study evaluated the efficacy of combination therapy using extracts of Annona senegalensis and Eucalyptus camaldulensis in treating T. b. brucei infected mice. A combination of extracts from the two plants in a 1:1 ratio cleared parasites from the blood of one mouse within 2 weeks and the mouse survived over 3 months without parasites. Histopathological examination of organs from the surviving mouse showed damage to the liver and kidneys. The study concludes that the combination of extracts has potential for developing drug combinations to overcome parasite resistance, though it caused long-term organ damage.
This chapter discusses various methods for classifying crude drugs, including alphabetical, taxonomic, morphological, pharmacological, chemical, chemotaxonomic, and serotaxonomic classification. The alphabetical classification method arranges crude drugs in alphabetical order by their Latin, English, or local names and is the simplest approach. However, it does not consider the biological relationships between drugs. The taxonomic classification method classifies drugs according to their taxonomic ranks, from kingdom to species, providing information on their biological relationships but it can be complex. Other classification methods organize drugs based on their morphology, pharmacological effects, chemical constituents, or time of collection. Each method has its own strengths and weaknesses.
Pharmacognosy is the study of drugs from natural sources. It involves identifying plants and other organisms used for medicines, assessing the safety and efficacy of herbal medicines, and securing supply of natural products. The scope of pharmacognosy has expanded from a focus on medicinal plants to also include microorganisms, marine organisms, and animal products. Proper identification and classification of biological sources is important in pharmacognosy and relies on binominal nomenclature systems developed by Linnaeus.
Crude drugs are obtained from six major natural sources: plants, animals, minerals, microbes, tissue culture and recombinant DNA technology, and semi-synthetic processes. Plant sources provide the oldest and most abundant crude drugs, with all plant parts used including leaves, flowers, fruits, seeds, roots, and bark. Animal sources include hormones, enzymes and organs from animals. Marine sources provide compounds from algae, fungi and marine organisms. Microbes are a source of antibiotics and vaccines. Tissue culture and recombinant DNA technology allow production of drugs like antibiotics, hormones and analgesics. Semi-synthetic processes modify natural compounds into new drugs.
Sources of crude drugs (natural)
Drugs obtained from Plants, Animals, Marine, Microorganism, Mineral and from Biotechnology (plant tissue culture) are covered in the presentation
his guideline should be read in conjunction with other ICH guidelines relevant to the
conduct of clinical trials (e.g., E2A (clinical safety data management), E3 (clinical study
reporting), E7 (geriatric populations), E8 (general considerations for clinical trials), E9
(statistical principles), and E11 (pediatric populations)).
This ICH GCP Guideline Integrated Addendum provides a unified standard for the European
Union, Japan, the United States, Canada, and Switzerland to facilitate the mutual acceptance
of data from clinical trials by the regulatory authorities in these jurisdictions. In the event of
any conflict between the E6(R1) text and the E6(R2) addendum text, the E6(R2) addendum
text should take priority.
This document provides an overview of pharmacognosy including:
- Pharmacognosy is the study of drugs from natural sources like plants and animals.
- It covers the extraction of drugs, history of herbal medicine, and scope of pharmacognosy as a field.
- Key terms are defined like crude drugs, extraction processes, solvents used, and important plant-derived drugs and their pharmacological activities.
- The history of herbal medicine is discussed from ancient civilizations in Mesopotamia, Egypt, India, and other regions.
- Extraction processes like infusion, decoction, and maceration are outlined along with solvents like water and alcohol.
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The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
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- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
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1. IOSR Journal of Pharmacy
Vol. 2, Issue 3, May-June, 2012, pp.345-363
Immunogenicity of Biopharmaceuticals
D.K.Das
Post Graduate Department of Biotechnology, T.M.Bhagalpur University, Bhagalpur-812007.
ABSTRACT
Modern biotechnology has resulted in a resurgence of interest in the production of new therapeutic agents using botanical
sources. With nearly 500 biotechnology products approved or in development globally, and with production capacity limited,
the need for efficient means of therapeutic protein production is apparent. Through genetic engineering, plants can now be
used to produce pharmacologically active proteins, including mammalian antibodies, blood product substitutes, vaccines,
hormones, cytokines, and a variety of other therapeutic agents. Efficient biopharmaceutical production in plants involves the
proper selection of host plant and gene expression system, including a decision as to whether a food crop or a non-food crop
is more appropriate. Product safety issues relevant to patients, pharmaceutical workers, and the general public must be
addressed, and proper regulation and regulatory oversight must be in place prior to commercial plant-based biopharmaceutical
production. Plant production of pharmaceuticals holds great potential, and may become an important production system for a
variety of new biopharmaceutical products.
INTRODUCTION
The use of plants or their extracts for the treatment of human disease predates the earliest stages of recorded civilization,
dating back at least to the Neanderthal period. By the 16th century, botanical gardens provided a wealth of materia medica for
teaching therapeutic use; and herbal medicine flourished until the 17th century when more scientific ‘pharmacological’
remedies were discovered (1). Subsequently, the active principle in many medicinal plants was identified and in many cases,
purified for therapeutic use. Even today, about one-fourth of current prescription drugs have a botanical origin (1).
Medicinal plants play a vital role for the development of new drugs. They produce different drugs for the remedy of
different diseases in human beings. These are ectoposide; E-guggulsterone, teniposide, nabilone, plaunotol, Z-guggulsterone,
lectinan, artemisinin and ginkgolides appeared all over the world. 2% of drugs were introduced from 1991 to 1995 including
paciltaxel, toptecan, gomishin, irinotecan etc. Plant based drugs provide outstanding contribution to modern therapeutics; for
example: serpentine isolated from the root of Indian plant Rauwolfia serpentina in 1953, was a revolutionary event in the
treatment of hypertension and lowering of blood pressure. Vinblastine isolated from the Catharanthus rosesus (53) is used
for the treatment of Hodgkins, choriocarcinoma, non-hodgkins lymphomas, leukemia in children, testicular and neck cancer.
Vincristine is recommended for acute lymphocytic leukemia in childhood advanced stages of Hodgkins, lymophosarcoma,
small cell lung, cervical and breast cancer. (54). Phophyllotoxin is a constituent of Phodophyllum emodi currently used
against testicular, small cell lung cancer and lymphomas. Indian indigenous tree of Nothapodytes nimmoniana (Mappia
foetida) are mostly used in Japan for the treatment of cervical cancer (Table 1).
Table 1 Some of the important medicinal plants used for major modern drugs for cancer
Plant name/family Drugs Treatment
Cathranthus rosesus L. (Apocynaceae) Vinblastine and vincristine Hodgkins, Lymphosarcomas
and children leukemia.
Podophyllum emodi Wall. (Beriberidaceae) Podophyllotaxin, Testicular cancer, small cell
lung cancer and lymphomas.
Taxus brevifolius (Taxaceae) Paciltaxel, taxotere Ovarian cancer, lung cancer
and malignant melanoma.
Mappia foetida Miers. Comptothecin, lrenoteccan and Lung, ovarian and cervical
topotecan cancer.
Comptotheca acuminata Quinoline and comptothecin used in Japan for the treatment
alkaloids of cervical cancer
Juniperus communis L. (Cupressaceae) Teniposide and etoposide Lung cancer
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Plant derived drugs are used to cure mental illness, skin diseases, tuberculosis, diabetes, jaundice, hypertension and cancer.
Medicinal plants play an important role in the development of potent therapeutic agents. Plant derived drugs came into use in
the modern medicine through the uses of plant material as indigenous cure in folklore or traditional systems of medicine.
More than 64 plants have been found to possess significant antibacterial properties; and more than 24 plants have been found
to possess antidiabetic properties, antimicrobial studies of plants (55), plant for antiodotes activity - Daboia russellii and
Naja kaouthia venom neutralization by lupeol acetate isolated from the root extract of Indian sarsaparilla Hemidesmus
indicus R.Br (56). Which effectively neutralized Daboia russellii venom induced pathophysiological changes (57). The
present investigation explores the isolation and purification of another active compound from the methanolic root extract of
Hemidesmus indicus, which was responsible for snake venom neutralization. Antagonism of both viper and cobra venom and
antiserum action potentiation, antioxidant property of the active compound was studied in experimental animals. Recently,
(58) from this laboratory reported that an active compound from the Strychnus nux vomica seed extract, inhibited viper
venom induced lipid peroxidation in experimental animals. The mechanism of action of the plant derived micromolecules
induced venom neutralization need further attention, for the development of plant-derived therapeutic antagonist against
snakebite for the community in need. However, the toxicity of plants has known for a long period of time, and the history of
these toxic plants side by side with medicinal ones are very old and popular worldwide, they considered the major natural
source of folk medication and toxication even after arising of recent chemical synthesis of the active constituents contained
by these plants (59, 60, 61). Traditional medicine is the synthesis of therapeutic experience of generations of practicing
physicians of indigenous systems of medicine. Traditional preparation comprises medicinal plants, minerals and organic
matters etc. Herbal drug constitutes only those traditional medicines that primarily use medicinal plant preparations for
therapy. The ancient record is evidencing their use by Indian, Chinese, Egyptian, Greek, Roman and Syrian dates back to
about 5000 years (Table 2).
Table 2: Plant derived ethnotherapeutics and traditional modern medicine
S.No. Drug Basic investigation
1. Codeine, morphin Opium the latex of Papaver somniferum used by ancient Sumarians.
Egyptaians and Greeks for the treatment of headaches, arthritis and
inducing sleep.
2 Atropine, hyoscyamine Atropa belladona, Hyascyamus niger etc., were important drugs in
Babylonium folklore.
3 Ephedrine Crude drug (astringent yellow) derived from Ephedra sinica had been
used by Chinese for respiratory ailments since 2700 BC.
4 Quinine Cinchona spp were used by Peruvian Indians for the treatment of
fevers
5 Emetine Brazilian Indians and several others South American tribes used root
and rhizomes of Cephaelis spp to induce vomiting and cure dysentery.
6 Colchicine Use of Colchicum in the treatment of gout has been known in Europe
since 78 AD.
7 Digoxin Digitalis leaves were being used in heart therapy in Europe during the
th
18 century
Modern biotechnology has led to a resurgence of interest in obtaining new medicinal agents from botanical sources. Through
genetic engineering (GE), plants can now be used to produce a variety of proteins, including mammalian antibodies, blood
substitutes, vaccines and other therapeutic entities (2). Recently, the production of foreign proteins in genetically engineered
(GE) plants has become a viable alternative to conventional production systems such as microbial fermentation or mammalian
cell culture. GE plants, acting as bioreactors, can efficiently produce recombinant proteins in larger quantities than those
produced using mammalian cell systems (3). Plant-derived proteins are particularly attractive, since they are free of human
diseases and mammalian viral vectors. Large quantities of biomass can be easily grown in the field, and may permit storage of
material prior to processing. Thus, plants offer the potential for efficient, large-scale production of recombinant proteins with
increased freedom from contaminating human pathogens.
During the last two decades, approximately 95 biopharmaceutical products have been approved by one or more regulatory
agencies for the treatment of various human diseases including diabetes mellitus, growth disorders, neurological and genetic
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maladies, inflammatory conditions, and blood dyscrasias (4, 6). -Some 500 agents are believed to be in development world-
wide, with some 370 biopharmaceuticals in the US, including 178 agents directed against cancer or related conditions, 47
against infectious diseases, and the remainder for a variety of important medical conditions (Figure 1) (6). Among these,
therapeutic entities are recombinant proteins, monoclonal antibodies, antisense oligonucleotides, and a variety of other protein
agents such as hormones and immunomodulating drugs (Figure 2). This rapid increase in the number of new protein and
peptide drugs reflects rapid advances in molecular biology, highlighted by the success of the human genome project that, in
turn, will help to identify many additional opportunities for therapeutic intervention. Unfortunately, our capacity to produce
these proteins in the quantities needed is expected to fall far short of demand by the end of the current decade (7). While none
of the commercially available products are currently produced in plants, those biotechnology products, which are comprised
of proteins, and possibly also DNA-based vaccines, are potential candidates for plant-based production.
Figure 1 Number of biopharmaceuticals under development, by disease class as of 2003 (6)
Figure 2. Number of biopharmaceuticals under development, by type of agent (6)
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Advances in plant biotechnology have already resulted in plants that produce monoclonal antibodies or other therapeutic
proteins, or that may serve as a source of edible vaccines. Research now underway will almost certainly result in GE plants
designed to produce other therapeutic agents including hormones (e.g. insulin, somatotropin, erythropoietin), blood
components, coagulation factors, and various interferons, and may well avoid critical limitations in production capacity.
Transgenic pharmaceutical plants are primarily modified by the introduction of novel gene sequences, which drive
the production of ‘designer’ proteins or peptides. These proteins or peptides possess therapeutic value themselves, have
properties that allow them to be used as precursors in the synthesis of medicinal compounds, or may serve as technical
enzymes in pharmaceutical production. This review will attempt to catalogue the potential therapeutic applications of plant
biotechnology and to address concerns related to the safety and efficacy of these agents in relation to human health and to
specific disease states.
The why and how of plant biotechnology
Plant biotechnology can lead to the commercial production of pharmacologically important Therapeutic proteins, in many
cases are fully functional and nearly identical to their mammalian counterparts (2). The application of plant biotechnology to
produce hormones or other biologically active molecules began nearly 20 years ago, with a crucial advance being the
expression of functional antibodies in plants, thereby demonstrating that plants could produce complex proteins of therapeutic
significance (2). While bacteria are inexpensive and convenient production systems for many proteins (e.g. human insulin),
they are incapable of the post-translational modification and assembly steps required for biological activity in more complex
multi-component proteins such as antibodies (2). Plants exhibit an effective eukaryote protein synthesis pathway, and by
combining currently available gene expression systems with appropriate acreage, plants can readily produce ton quantities of
protein (2). Unlike mammalian cell systems, which can sometimes express pathogenic viral agents, plant systems are
intrinsically free of mammalian pathogens (8). Thus, plant expression systems may offer advantages over bacterial and
mammalian cell culture systems (Table 3) (2).
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Table 3. Comparison of recombinant protein production in plants, yeast and mammalian systems
Biopharmaceutical production in plants necessitates a series of careful decisions regarding three critical areas: (i) the gene
expression system to be used, (ii) the location of gene expression within the plant, and (iii) the type of plant to be used.
There are a number of gene expression strategies that can be used to produce specific proteins in plants. With transient
expression (TE), a gene sequence is inserted into plant cells using plant viruses, ballistic (gene-gun), or other methods,
without incorporation of the new genetic material into the plant chromosome. TE systems can be rapidly deployed and can
produce large amounts of protein (2) but because non-chromosomal DNA is not copied with the process of mitosis or meiosis,
gene expression is neither permanent nor heritable. While TE systems are very useful for research and development, and may
be useful for drug production, they require the fresh production of transformed plants with each planting and may be less
attractive for long-term or high-volume protein production.
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Alternatively, the primary plant chromosome can be altered to allow for the permanent and heritable expression of a
particular protein, i.e. allow the creation of plants, which produce seed carrying the desired modification. This can be done
using Agrobacterium tumefaciens, a pathogen of plants that, in nature, transfers genetic material to the plant chromosome. By
modifying the genetic content of Agrobacterium, desired genes can be readily inserted into many kinds of plants, especially
dicots such as soybean.(2, 9) Genetic materials can also be coated onto small metallic pellets and introduced into cells
ballistically using a ‘gene-gun’(9). This latter system is useful for a wide variety of plant species. While permanent
modification of the plant genome is more costly and time-consuming, it offers the clear advantage of stable, ongoing protein
production with repeated planting alone.
Finally, systems exist that modify chloroplast DNA in plants and that can lead to heritable changes in protein
expression (3). Plant chloroplasts may play a critical role in the future development of biopharmaceuticals. These tiny
energy-producing organelles appear to possess advantages over nuclear transformation, particularly given that each cell may
carry hundreds or thousands of such organelles, resulting in the ability to sustain very high numbers of functional gene copies.
Transgenic tobacco chloroplasts, for example, can produce human somatotropin at protein levels over a hundred-fold higher
than do their nuclear transgenic counterparts, with production of somatotropin and Bt insecticidal protein representing 7% and
45% of total plant protein production (10). In the final analyses, the selection of a plant expression system is influenced by
cost, safety, and production factors.
Consideration must also be given to where within the plant a pharmaceutical protein is to be produced. Current
technology allows gene expression and protein production in either the green matter of the plant (whole plant expression) or
selectively in the seed or other tissues through the use of selective promoter systems (11). Production in green mass can
produce large amounts of protein (3). Green matters are highly physiologically active and protein levels may be poorly
preserved if materials are not rapidly dried or otherwise inactivated (8, 11). Thus, unless a protein or peptide is highly stable,
green matter production may result in poor protein recovery and usually requires immediate processing. Tuber or root
production, while feasible, shares many of the characteristics of green matter production systems. Unlike green matter, seeds
generally contain fewer phenolic compounds and a less complex mixture of proteins and have specifically evolved to provide
for stable, long-term storage of proteins and other materials in order to assure successful, delayed germination (3). Seeds are
therefore an extremely attractive production medium, which can also provide the flexibility to store product for delayed
processing.
It is also necessary to decide which plant species to transform for production of a specific pharmaceutical product.
While nearly any plant could theoretically be transformed, practical considerations suggest the use of plants with which we
are most familiar, and which already have well-established techniques for genetic transformation, high volume production,
harvest, and processing. For green matter production, tobacco has usually been the material of choice, largely because of its
highly efficient production of biomass (2) although other systems such as alfalfa and even duckweed show promise (12). For
seed production, a plant optimized for large seed and high protein production is clearly preferred. Food crop plants have been
bred specifically to produce highly productive stands of high-protein seed for which harvesting, processing, and storage
technologies are already available. Further, techniques for genetic modification of these plants are well understood, and the
extensive history of cultivation and genetic research provides both an understanding of genetic stability and a pool of genetic
resources (such as the ability to control pollination using the classical C-male-sterile gene in corn), which facilitate
production. This makes food crops highly attractive, with soybean and maize being the obvious choices. This choice, while
highly rational, does lead to the potential for the unintended presence of therapeutic protein in human food, and thus
necessitates carefully controlled production to avoid the inadvertent presence of therapeutic material in foods, as discussed
below.
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Production, safety and efficacy
Drug research is a unique multi-disciplinary process leading to the development of novel therapeutic agents for disease states
that have unmet needs (13). The search for new biopharmaceuticals is driven by a medical need and by the perceived
likelihood of technological success, as determined by both therapeutic efficacy and safety parameters. There are several
factors to consider for the safety testing of new biopharmaceuticals (14). Because of the protein nature of most
biopharmaceutical products; few non-allergic adverse reactions other than those attributable to the primary pharmacological
activity are anticipated. Nevertheless, both Good Laboratory Practice and Good Manufacturing Practice, as established for
other modes of pharmaceutical production, are essential to plant made pharmaceuticals. Before experimental or clinical use is
initiated, it is critical to have fully characterized, contaminant-free materials, as well as appropriate quality assurance so that
both the product itself and the therapeutic results will be reproducible. New pharmaceutical agents derived through plant
biotechnology must be subjected to the same purity, quality-control, and safety standards as materials derived from bacterial
or mammalian cell systems or from other traditional sources such as vaccine production.
Sites used for the cultivation of genetically modified plants have in some cases been disrupted or destroyed by
individuals opposed to the use of plant biotechnology, raising additional security concerns. In part, these concerns can be
addressed via increased field site monitoring and security, and the use of enclosed environments (greenhouses) for small-scale
operations. The relatively small scale and favorable economics of biopharmaceutical operations allow the placement of field
operations in geopolitical locations selected for optimal security, with subsequent shipping of raw or processed materials.
Transgenic plants have the added safety feature of freedom from human or animal pathogens (8). Additionally, plant
cells are capable of producing complex proteins while largely avoiding the presence of endotoxins in bacterial systems.
Endotoxins are often difficult to remove and can contaminate a final product. Thus, there is intrinsic safety and value in using
plants as a source of recombinant protein (15). However, as with all plant-derived pharmaceuticals, appropriate measures
must be taken to eliminate undesirable plant-derived proteins or other biomolecules and to control the presence of fungal
toxins or of pesticides used in plant production (11).Safety evaluations must consider possible non-target organ responses as
well as the entire gamut of anticipated and unanticipated side effects as with any bio-pharmaceutical product. Somewhat
unique to plant-produced pharmaceuticals are potential effects on non-target species such as butterflies, honeybee, and other
wildlife at or near the growing sites. Fortunately, in most instances, the effect on non-target species is limited by the fact that
proteins are a normal part of the diet, are readily digested, and are degraded in the environment. Further, many
biopharmaceuticals proteins, especially antibodies, are highly species-specific in their effects.
Pharmaceutical production in plants may create the potential for the flow of pharmaceutical materials into the human
food chain, especially when food crops are used. This could occur as a result of inadvertent cross-contamination of foodstuffs,
through spontaneous growth of genetically engineered plants where they are not desired, or by virtue of pollen flow with
some plants (e.g. corn), but not others (e.g. potato). While some have therefore suggested restricting pharmaceutical
production to non-food crops such as tobacco, it is the food crops that present the greatest opportunities for efficient
production of biopharmaceuticals and that will be most useful for the production of edible vaccines. Because of the potential
for adventitious presence in food, care must be exercised in the production of biopharmaceuticals in food crops. Fortunately,
acreage requirements for pharmaceutical production are limited, with metric ton protein production being feasible with >5000
acres of corn (9). This allows for production under tightly controlled conditions which include production in areas of the
country where the crop in question is not routinely grown, the use of physical isolation distances and temporal separation to
prevent cross-pollination with food crops, the use of de-tasseling and/or male-sterile traits to control pollen flow, dedicated
harvest and storage equipment, and controlled processing separate from all food crops. Unlike commodity crops, plant
production of pharmaceuticals should be performed only under tightly controlled conditions similar to those of other
pharmaceutical manufacturing; and industry, USDA, FDA, and international organizations have developed production
standards jointly (12). These standards are enforced in the US through USDA and FDA, and compliance is further
encouraged by the desire of producers to avoid potential liability and infractions. FDA required Good Manufacturing Practice
necessitates extensive control of field access, harvest, and product disposition.
While production controls are necessary and appropriate, it should be kept in mind that the majority of therapeutic
proteins are not anticipated to have any pharmacological activity when ingested, and are thus unlikely to present a safety issue
in the event of accidental contamination of foodstuffs. For example, antibodies, insulin, growth hormone, and most other
proteins produce few, if any, systemic pharmacological effects by the oral route. This does not preclude the possibility of
local effects on the gastro-intestinal tract or the possibility of immunological effects, as seen in the context of oral vaccines,
where such an effect is introduced by design. In fact, one plant-derived antibody directed against epithelial cellular adhesion
molecules was withdrawn from clinical development as a result of gastro-intestinal side effects believed to be due to binding
to the relevant antigen, which is expressed in the GI tract (8). This is a result of the antigenic specificity of the antibody, and
is not attributable to the plant-derived nature of the molecule. While a case-by-case determination of risk will be necessary
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when considering proteins for food crop applications, it appears that the majority of proteins would present no great hazard to
the public in the event that control technologies should fail to be fully effective.
The production of pharmaceuticals in plants
There are a number of recent comprehensive review articles pertaining to production technologies used for molecular farming
in plants (3, 8, 9, 11, 15). The first commercially produced biopharmaceutical, recombinant human insulin from bacteria, was
produced in 1982; an event which coincides roughly with the first development of a genetically modified plant in 1984 (16,
17). This latter development was followed rapidly with a demonstration of the potential of plants for pharmaceutical
production with plant expression of human growth hormone fusion protein (18), interferon (19), monoclonal antibodies (20),
and serum albumin (21). Since that time, numerous demonstrations of pharmaceutical production in plants have occurred and
are described below within three broad categories of therapeutics: antibodies, vaccines, and other therapeutics.
Antibodies
Monoclonal antibodies (mAbs) have been critical both for the development of biotechnology itself and as products for both
therapeutic and diagnostic purposes. Traditional therapeutic monoclonal antibodies have been derived from mice. These
proteins were readily identified by the human immune system as foreign, limiting the utility of these antibodies for
therapeutic use, especially with repeated dosing (22). Even in the absence of anaphylaxis or serum sickness, the occurrence
of neutralizing antibodies that inactivate the drug often precluded further therapeutic use. However, recombinant technologies
have allowed murine antibodies to be replaced with partially humanized or chimeric antibodies, and now allow the production
of fully human antibodies (22). The latter may be derived from mice carrying the human immunoglobulin genes or produced
using yeast or other gene-expression array technologies (9, 22). Recombinant technology can also be used to selectively
‘evolve’ an antibody gene to produce higher affinity binding (affinity maturation) (9). Thus, compared with earlier
monoclonal antibodies, current recombinant antibodies exhibit reduced immunogenicity and increased biological activity (22,
23). Recently, the first fully human therapeutic monoclonal antibody has been commercialized (Humira, Adalimumab,
Abbott Laboratories), and one would anticipate a low rate of neutralizing antibody development.
Currently, there are over a dozen FDA-approved mAbs, and as many as 700 therapeutic Abs may be under
development (9). Plants now have potential as a virtually unlimited source of mAbs, referred to by some as ‘plantibodies’.
Tobacco plants have been used extensively for antibody expression systems. However, several other plants have been used
including potatoes, soybeans, alfalfa, rice and corn. Antibody formats can be full-size, Fab fragments, single-chain antibody
fragments, bi-specific scFv fragments, membrane anchored scFv, or chimeric antibodies (see Table 4) (2). Plant cells, unlike
mammalian cell expression systems, can express recombinant secretory IgA (sIgA). sIgA is a complex multi-subunit antibody
that may be useful in topical immunotherapy, and has been successfully expressed in the tobacco plant. Transgenic soybeans
are capable of producing humanized antibodies against herpes simplex virus-2. GE corn reportedly is capable of producing
human antibodies at yields of up to a kg per acre (9) and has been demonstrated to preserve antibody function through five
years of storage under ordinary conditions.
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Table 4. Recombinant antibodies expressed in transgenic plants
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CEA, carcinoembryonic antigen; ER, endoplasmic reticulum; AMCV, artichoke mottle crinkle virus; TMV, tobacco mosaic
virus; RKN, root knot nematode; BNYVV, beet necrotic yellow vein virus; HSV-2, herpes simplex virus-2; scFv-IT, scFv-
bryodin-immunotoxin. N. benthamiana, tobacco (Nicotiana)-related species, A. thaliana, Arabidopsis, an experimental
species
Antibodies derived from plants have a multitude of applications, including binding to pathogenic organisms, binding to serum
or body fluid effector proteins (e.g. interleukins), binding to tumour antigens to deliver imaging or anti-tumour agents, or
binding to a cellular receptor site to up- or down-regulate receptor function. However, plant glycosylation patterns differ from
those in mammalian systems, and glycosylation is essential for antibody-mediated activation of complement or the initiation
of cellular immune responses (11, 22). Plantibodies may carry plant glycoproteins or may be non-glycosylated as a result of
genetically deleting glycosylation sites, but are incapable of inducing the latter phenomena in either case (22). This does not
appear to be a major limitation, however, since therapeutic applications of monoclonal antibodies are often mediated by
binding and inactivation of proteins or receptor molecules and do not require complement or cell-mediated immunity. While
glycosylation sequences are poorly immunogenic and hence unlikely to precipitate immunological adverse reactions (8) the
presence of mammalian glycosylation sequences not required for therapeutic function may only serve to produce undesired
complement- or cell-mediated side effects.
As of 2001, four antibodies expressed in plants had shown potential to be useful as therapeutics (3). A chimeric
secretory IgG/IgA antibody effective against a surface antigen of Streptococcus mutans has been expressed in tobacco, and
has been demonstrated to be effective against dental caries (24). Soybeans can express a humanized anti-herpes simplex virus
(HSV), which has been effective in preventing the transmission of vaginal HSV-2 in animals (25). Rice and wheat expression
systems can produce antibodies against carcinoembryonic antigen, which may be useful for in vivo tumor imaging (26).
Finally, a plant viral vector has been used to produce a transiently expressed tumor-specific vaccine in tobacco for the
treatment of lymphoma (27). Currently, seven plant-derived antibodies have reached the advanced stages of clinical product
development (8). These include products directed at the treatment and/or diagnosis of cancer, dental caries, herpes simplex
virus, and respiratory syncytial virus. No ‘plantibodies’ have currently reached the commercialized stage, although at least
one product has been tested clinically, and several have been examined in vitro and in animal systems and appear to be
equivalent to mammalian-cell-derived analogues (28). Given the high levels of production, purification cost, apparent
efficacy, and low immunogenicity of recombinant human antibodies derived from plants, plants appear to hold great potential
for future production of monoclonal antibodies.
Vaccines
There has been considerable interest in developing low-cost, edible (i.e. oral) vaccines. (29, 32). Traditional edible vaccines,
as for polio, use whole, attenuated organisms or semi-purified materials to induce both systemic (Ig-G-mediated) and local
membrane (Ig-A-mediated) immunity. Plant vaccines can express entire selected proteins, but the use of DNA encoding only
desired antigenic sequences from pathogenic viruses, bacteria and parasites has received considerable attention (33). Key
immunogenic proteins or antigenic sequences can be synthesized in plant tissues and subsequently ingested as edible subunit
vaccines (30, 31, 33). The mucosal immune system can induce protective immune responses against pathogens or toxins, and
may also be useful to induce tolerance to ingested or inhaled antigens (30, 31). The production of secretory Ig-A (sIg-A) and
provocation of specific immune lymphocytes can occur in mucosal regions, and these regions take on special importance in
the development of edible vaccines. Aside from intrinsic low production cost, plant-based vaccines offer a number of unique
advantages, including increased safety, stability, versatility, and efficacy (34). Plant produced vaccines can be grown locally
where needed, avoiding storage and transportation costs. Relevant antigens are naturally stored in plant tissue, and oral
vaccines can be effectively administered directly in the food product in which they are grown, eliminating purification costs
(30, 34). In many instances, it appears that refrigeration will not be needed to preserve vaccine efficacy, removing a major
impediment to international vaccination efforts of the past (30, 33). Plants engineered to express only select antigenic
portions of the relevant pathogen may reduce immunotoxicity and other adverse effects, and plant-derived vaccines are free of
contamination with mammalian viruses. Finally, the development of multi-component vaccines is possible by insertion of
multiple genetic elements or through cross-breeding of transgenic lines expressing antigens from various pathogenic
organisms.
There are, however, some limitations associated with the use of transgenic plants for vaccine production (10). A
major limitation of the expression of recombinant antigens in transgenic plants is obtaining a protein concentration adequate
to confer total immunity, given varying protein expression among and within the various plant species. Tight control of
expression yields will likely be necessary to reduce variability and assure consistent, effective immunization (10). During the
last decade, nearly a dozen vaccine antigens have been expressed in plants (Table 5) (2). Transgenic potatoes can produce
antigens of enterotoxigenic E. coli heat labile enterotoxin B subunit, and is effective in immunizing against viruses and
bacteria that cause diarrhoea. Still other ‘edible vaccines’ are under development for rabies, foot and mouth disease
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(veterinary), cholera, and autoimmune diabetes. Transgenic lupin and lettuce plants can express hepatitis B surface antigen.
Efforts are underway to develop an ‘edible vaccine’ against the measles virus using the tobacco plant. A plant-based oral
subunit vaccine for the respiratory syncytial virus (RSV) using either the apple or the tomato is under development (30).
Table 5. Recombinant vaccines expressed in plants
* Plant Virus – can be expressed in multiple plant species
The plant species to be used for the production and delivery of an oral vaccine can be specifically selected to achieve desired
goals. A large number of food plants (e.g. alfalfa, apple, asparagus, banana, barley, cabbage, canola, cantaloupe, carrots,
cauliflower, cranberry, cucumber, eggplant, flax, grape, kiwi, lettuce, lupins, maize, melon, papaya, pea, peanut, pepper,
plum, potato, raspberry, rice, service berry, soybean, squash, strawberry, sugar beet, sugarcane, sunflower, sweet potato,
tomato, walnut, and wheat) have been transformed (29). Many of the high volume, high acreage plants such as corn,
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soybeans, rice, and wheat may offer advantages. Corn, since it is a major component in the diet of the domestic animal, is a
good candidate for vaccine production. In humans, particularly infants, the plant of choice to produce the vaccine might be
the banana. Bananas are a common component of many infant diets and can be consumed uncooked, thus eliminating the
possibility of protein denaturation due to high temperatures. Unfortunately, it is relatively difficult to create transgenic
bananas and the production time is longer than for certain other food crops. Cereals and other edible plants are advantageous
for vaccine production over plant species such as tobacco because of the lower levels of toxic metabolites. It is evident that
there are numerous opportunities to identify and develop low-cost plant derived vaccine materials, including edible plant-
based vaccines.
Other therapeutic agents
A wide variety of other therapeutic agents have been derived from plants (Tables 6, 7), including hormones (somatotropin),
enzymes, interleukins, interferons (IFN) and human serum albumin (HSA) (2, 23). Similar biotherapeutic agents have also
been expressed from mammalian and bacterial cell systems (4). There is a worldwide demand for HSA, and plant production
would offer the advantage of freedom from contamination with human pathogenic viruses. Modified rice plants are capable of
producing human alpha-1-antitrypsin, a protein that may realize therapeutic potential in emphysema and hepatic diseases.
Hirudin, originally isolated from leeches, is a blood anticoagulant that can now be expressed from oilseed rape, from tobacco
and from mustard. Transgenic potato plants can encode for at least two subtypes of human INF, some of which may moderate
certain cancers and diseases caused by viral agents.
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Table 6. Biopharmaceuticals derived from transgenic plants
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Table 7. Selected pharmaceutical proteins expressed in transgenic plants
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Erythropoietin (EPO) has also been expressed in transgenic tobacco plants. Erythropoietin, a glycoprotein used to treat
anaemias, was commercialized from mammalian systems nearly 20 years ago. Blood substitutes such as human haemoglobin
have long been pursued, and human haemoglobin derived from transgenic tobacco is being tested to ensure the molecule's
function and oxygen-carrying capacity (35). In general, the levels of pharmaceutical proteins produced by transgenic plants
have been low, often <1% of total soluble protein. While this is quite sufficient to allow for economical production of highly
active pharmaceutical molecules, improved technologies for high level expression of protein will be probably needed to allow
practical production of high volume human replacement proteins such as HSA (Human serum albumin) (3) haemoglobin or
blood coagulation factors.
Basis for immunogenicity to biopharmaceuticals
Most biopharmaceuticals induce immune responses (immunogenicity), which in many cases do not have clinically relevant
consequences. However, in some cases the consequences can be severe and potentially lethal, causing a loss of efficacy of the
drug or even worse, leading to autoimmunity to endogenous molecules. In case of exogenous protein products (neo-antigens
or non-self antigens), such as biopharmaceuticals derived from non-human origin (microbial, plant or animal), the immune
response to the foreign protein leads to neutralizing antibodies. This immune response is mediated by T cells and occurs as a
fast reaction after first meeting the antigen.
The immune response to endogenous proteins of human origin (self-antigen), such as human recombinant DNA
products, leads to binding antibodies. B cells through the breakdown of immune tolerance mediate this response, and the
reaction develops slowly and disappears after treatment withdrawal.
The theoretical basis for immunogenicity to biopharmaceuticals is based on their foreign nature, being of exogenous
origin (neo-antigens or non-self antigens), or their similarity to self molecules (self antigens). In both cases, it is the activation
of antibody-secreting B cells that leads to the clinical manifestation of immunogenicity.
There are two ways in which such immunogenicity can occur. First impurities, such as endotoxins or denatured
proteins within a biopharmaceutical may provide a second, so-called ‘danger’ signal to T cells that may then send activating
signals to B cells and hence, break B-cell tolerance. Second, B-cell tolerance can be broken via a T-cell independent response.
If a biopharmaceutical for instance is not uniformly soluble it can form aggregates (Figure 3). The immune system may
confuse these aggregates with viruses, and B cells are activated to proliferate and produce auto-reactive binding antibodies.
Fig. 3
Influence
of form of
antigen on
B cell
response
type (A)
maintaining
self-
tolerance or
(B)
breaking
self-
tolerance.
BCR, B
cells
receptor.
Factors contributing to immunogenicity
Product-related factors
There are documented product- and host-related factors leading to immunogenicity of biopharmaceuticals (36). Product-
related factors include structural properties, such as protein sequence, the presence of exogenous or endogenous epitopes and
the degree of glycosylation influencing protein degradation, exposure of antigenic sites and solubility. The higher
immunogenicity of an Escherichia coli-derived IFNß product has been linked to the lack of glycosylation compared with
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other Chinese hamster ovary (CHO) cell-derived products (37). Other product-related factors influencing immunogenicity are
formulation and storage, downstream processing and the level of impurity or presence of contaminants. Evidence for the
importance of these factors can be found in the reported variation in antigenicity of IFNß products produced at different
manufacturing sites (38). Changing the formulation and storage of IFN 2a has been shown to lower immunogenicity (38).
Further documented examples include the effect of downstream processing on the immunogenicity of factor VIII and the
induction of antibodies against insulin and growth hormone due to product impurity (39, 40).
Host-relatedfactors
Several host-related factors affect the immunogenicity of a biopharmaceutical. The genetic predisposition of a patient may
influence the production of neutralizing antibodies. For example, the major histocompatibility complex (MHC) allele affects
host recognition of antigen in T-cell mediated responses. Alternatively, the genetic sequence encoding the endogenous
equivalent of the therapeutic protein may play a role. Haemophilia A patients treated with factor VIII have been shown to
have different probabilities of developing immunogenicity depending on their endogenous expression of the protein (41, 42).
Patients with genetic deletion of factor VIII recognized it as foreign and produced neutralizing antibodies against it. Patients
with genetic deletion of factor VIII recognized it as foreign and produced neutralizing antibodies against it. Concomitant
illnesses, particularly of the kidney and liver, may also influence immunogenicity. Autoimmune diseases predispose patients
to producing antibodies against therapeutic proteins. Dose and route of administration are important determinants. Higher
doses or prolonged duration of treatment increase exposure and thereby heighten the risk of developing immunogenicity.
Immunogenicity appears to be greater if the biopharmaceutical is administered subcutaneously (SC) or intramuscularly and
has decreasing severity with intravenous and local administration (43).
Consequence of immunogenicity to biopharmaceuticals
In many cases, the presence of antibodies has little or no biological and clinical consequence. However, even in case of well-
established innovator biopharmaceutical products, biological and clinical consequences of immunogenicity have been
observed. The most common biological effect is the loss of efficacy, as has been described for IFN and ß (40). The loss of
efficacy may be restored with increasing dose such as Factor VIII for haemophilia A patients (40). Clinical consequences
may be manifested in general immune effects, such as anaphylaxis, allergic reactions or serum sickness. These have been
relatively common historically but have become less common with the increasing availability of highly purified products and
more stringent regulation of established biopharmaceuticals. Major clinical impact is seen, however, if a natural protein with
essential biological activity is neutralized. Such consequences have been described in the case of megakaryocyte-derived
growth factor (MDGF), where antibodies against the biopharmaceutical also neutralized endogenous thrombopoietin leading
to severe thrombocytopenia (44). An upsurge in the incidence of antibody-mediated pure red cell aplasia (PRCA) observed
outside the US between 2000 and 2002 revealed that a small change in the formulation of a well-established innovator
product with extensive patient years experience may have significant clinical consequences (45,46). The PRCA cases were
associated with a breakdown of immune tolerance to erythropoietin treatment resulting in neutralizing antibody formation not
only against the recombinant protein, but also the native erythropoietin (47). The sharp increase in incidence occurred
primarily among those on SC epoetin (EPO ) therapy (marketed as Eprex®/Erypo® by Johnson & Johnson), and coincided
with replacement of human serum albumin as stabilizer by glycine and polysorbate 80 in 1998. Subsequent withdrawal of the
SC formulation of EPO led to a considerable decrease in the incidence of PRCA cases.
A number of possible mechanisms have been proposed to explain the observed upsurge of PRCA. The modification
in the drug formulation probably played a major role (47). The role of leachates has been investigated (48), although results
failed to show their significant effect in immune responses. This direction of investigation was based on the observation that
among patients receiving SC EPO from syringes with Teflon-coated stoppers, the incidence of PRCA was lower. The role of
micelles (polysorbate 80 plus EPO ) is currently under investigation (49). It is nevertheless likely that the immunogenicity of
this particular product has been enhanced by the way the product was stored, handled and administered. Most certainly a
combination of factors contributed to the reduced incidence of PRCA by 2003. The case of PRCA has two-fold relevance
with regard to quality and safety of biopharmaceutical and biosimilar products. Although the innovator product has been in
use for years, it took time until the link between the relatively small modification in the product formulation and the upsurge
of PRCA cases was established. The picture becomes even more complex when biosimilar products are considered. Even
when biosimilars are produced from the same genetic construct, using the same technique, formulation and packaging as the
innovator product, there is no guarantee that they are comparable with the reference product. Bioassays of follow-up EPO
preparations manufactured in India, Asia and South America show their dissimilarities compared with the innovator EPO
product, despite their claimed substitutability and bioequivalence.
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Measuring immunogenicity
Assessing the immunogenicity of biopharmaceuticals is becoming increasingly important with the emergence of biosimilar
agents. Essentially there are two main types of assays: the radioimmunoprecipitation assays (RIPA) and enzyme-linked
immunosorbent assays (ELISA) which determine binding antibodies, while bioassays identify the presence of neutralizing
antibodies (50). These assays are usually used in conjunction. Patient sera are first screened for the presence of binding
antibodies and, if positive, the presence of neutralizing antibodies is tested for with the more cumbersome bioassay.
When a biopharmaceutical has unique determinants, assays become highly product specific. One problem is that
quality assurance assays for biopharmaceuticals are less sensitive and precise than are tests for small molecules, hence it is
difficult to analyse impurities (36). The timing of sample collection may also influence assay results—immunogenicity
typically develops after prolonged treatment. No single technique is available to predict immunogenicity of a
biopharmaceutical product (51). Methods used in different laboratories undertaking bioassays vary not only according to how
antibody levels are determined but also the way results are reported. Comparison of assay results between studies, and
laboratory sites face immense difficulties without international standardization of the assay procedures and data presentation
(52).
Future directions
The use of plants as factories for the production of novel vaccines, antibodies and other therapeutic proteins will undoubtedly
continue to develop. Molecular farming may become the premier expression system for a wide variety of new
biopharmaceuticals and ‘plantibodies’. Important economic advantages will likely be realized as the technology continues to
evolve and improve. Efforts will need to focus on increasing yields, on scale-up of production, on distribution and handling of
transgenic plant material, and on the development and validation of production techniques, which effectively isolate
pharmaceutical production from human and animal food. Plant-derived biopharmaceuticals will need to meet the same safety
and efficacy standards as those products obtained from non-plant sources. There will be a need for continued vigilance to
safeguard the environment, ensuring that errant substances do not affect non-target organisms. Gene containment
methodologies will continue to develop, and there must be safeguards against the over-expression of potentially harmful
proteins in transgenic pollen. Undoubtedly, there will be a continuing debate about the use of transgenic food plants, as
opposed to non-food plants, for producing new pharmaceuticals. The advantages of recombinant plant DNA technology for
the production of antibodies, vaccines, other pharmaceuticals, and even high-volume plasma proteins are becoming
increasingly apparent. As the technology involves, it appears highly likely that plant-derived pharmaceuticals will play a
significant role in the future of clinical therapeutics.
ACKNOWLEDGEMENTS:
Author is highly grateful to University Grants Commission, New Delhi for providing grants to do work in this area of
Biopharmaceuticals.
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