Gene Therapy, Somatic cell gene therapy, germ line gene therapy, classical gene therapy, non-classical gene therapy, targets of gene therapy, barriers of gene therapy, ex vivo gene therapy, in vivo gene therapy, vectors for gene delivery, antisense therapy
in this presentation, what are the steps and strategies involved the gene cloning and i was focused only on the 1st two steps of gene cloning.they are generation of foreign DNA molecules and selection of suitable vectors.
Gene therapy of genetic disorders like hepatitis, neuroblastoma, thalassemiaD.R. Chandravanshi
Gene therapy is the modern techniques of treatment of various diseases and disorders.
Gene therapy is the introduction of genes into existing cells to prevent or cure a wide range of diseases.
It is a technique for correcting defective genes responsible for disease development.
Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
The first approved gene therapy experiment occurred on September1990 in US, when Ashanti DeSilva was treated for ADA-SCID.
Under the direction of William French Anderson, at the National Institutes of Health (NIH),
Gene Therapy, Somatic cell gene therapy, germ line gene therapy, classical gene therapy, non-classical gene therapy, targets of gene therapy, barriers of gene therapy, ex vivo gene therapy, in vivo gene therapy, vectors for gene delivery, antisense therapy
in this presentation, what are the steps and strategies involved the gene cloning and i was focused only on the 1st two steps of gene cloning.they are generation of foreign DNA molecules and selection of suitable vectors.
Gene therapy of genetic disorders like hepatitis, neuroblastoma, thalassemiaD.R. Chandravanshi
Gene therapy is the modern techniques of treatment of various diseases and disorders.
Gene therapy is the introduction of genes into existing cells to prevent or cure a wide range of diseases.
It is a technique for correcting defective genes responsible for disease development.
Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
The first approved gene therapy experiment occurred on September1990 in US, when Ashanti DeSilva was treated for ADA-SCID.
Under the direction of William French Anderson, at the National Institutes of Health (NIH),
A DNA library is a collection of cloned restriction fragments of the DNA of an organism.
Two kinds of libraries will be discussed: genomic libraries and complementary DNA (cDNA) libraries.
Genomic libraries ideally contain a copy of every DNA nucleotide sequence in the genome.
In contrast, cDNA libraries contain those DNA sequences that appear as mRNA molecules, and these differ from one cell type to another.
Gene transfer technology pharmacology biotechnology basic methods
Natural, physical, chemical methods of gene transfer.
Along with advantages and limitations, and applications.
INTRODUCTION OF GENE THERAPY, HISTORY OF GENE THERAPY, Process of gene therapy, Methods of gene therapy, Ex vivo gene therapy , In Vivo Gene Therapy , Uses of gene therapy, Target sites for Gene Therapy , Vectors for gene therapy , Viral Vectors, Non Viral Vectors,
A DNA library is a collection of cloned restriction fragments of the DNA of an organism.
Two kinds of libraries will be discussed: genomic libraries and complementary DNA (cDNA) libraries.
Genomic libraries ideally contain a copy of every DNA nucleotide sequence in the genome.
In contrast, cDNA libraries contain those DNA sequences that appear as mRNA molecules, and these differ from one cell type to another.
Gene transfer technology pharmacology biotechnology basic methods
Natural, physical, chemical methods of gene transfer.
Along with advantages and limitations, and applications.
INTRODUCTION OF GENE THERAPY, HISTORY OF GENE THERAPY, Process of gene therapy, Methods of gene therapy, Ex vivo gene therapy , In Vivo Gene Therapy , Uses of gene therapy, Target sites for Gene Therapy , Vectors for gene therapy , Viral Vectors, Non Viral Vectors,
Advances in biochemistry and molecular biology have helped to understand the genetic basis of inherited diseases.
Gene therapy was once considered a fantasy (imaginary).
It was a dream of the researchers to replace the defective genes with good ones and cure the genetic disorders.
Plant Disease Resistant And Genetic EngineeringShweta Jhakhar
Study the adverse effects of different viruses and other fungal diseases on the plants and their growth. Discuss the methods e.g. plant disease resistant and genetic engineering to protect the plants.
RNAi is a powerful, conserved biological process through which the small, double-stranded RNAs specifically silence the expression of homologous genes, largely through degradation of their cognate mRNA.
Gene therapy is an experimental treatment that involves introducing genetic material into a person’s cells to fight or prevent disease. Researchers are studying gene therapy for a number of diseases, such as severe combined immuno-deficiencies, hemophilia, Parkinson's disease, cancer and even HIV, through a number of different approaches (see video: 'Gene Therapy a new tool to cure human diseases'). A gene can be delivered to a cell using a carrier known as a “vector.” The most common types of vectors used in gene therapy are viruses. The viruses used in gene therapy are altered to make them safe, although some risks still exist with gene therapy. The technology is still in its infancy, but it has been used with some success.
In this slide, You will get to learn abut Gene Therapy and different types of gene therapy. Various method of Gene Therapy and Advantage & Disadvantage and Recent advances in Gene Therapy.
Lectins are carbohydrate-binding proteins or glyco-proteins binding selectively without the involvement of enzymes, Gene responsible for expression lection found in chromosome 10q11.2-q21
Found in plnats grains, legume, soy bean, kidney bean
Lectins recognize tumor marker which play important role for diagnosing tumor cell, screening tumour and able to detect subtle neoplastic changes
Gene therapy is the process of inserting genes into cells to prevent, treat or cure wide range of diseases. Gene therapy primarily involves genetic manipulations in animals or humans to correct a disease. Gene augmentation therapy: a DNA is inserted into the Genome to replace the missing gene product.Gene inhibition therapy: the antisense gene inhibits the expression of the dominant gene.
This presentation focuses on the science of Gene Therapy, the techniques of germ-line and somatic gene therapy and the mechanism of curing diseases and disorders using gene therapy. The presentation starts by discussing some common basic terms from genetics and moves on to the historical development of gene therapy techniques in chronological order. The different types of gene therapy techniques and their mechanisms have been discussed in detail subsequently. In concluding slides, some commercially available gene therapy products are mentioned and challenges of gene-therapy techniques have been highlighted.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
2. Genes
• Are carried on a chromosome
• The basic unit of heredity
• Encode how to make a protein.
• DNA RNA proteins
• Proteins carry out most of life’s function.
• When altered causes dysfunction of a protein
3. What is Gene Therapy
It is a technique for correcting defective
genes that are responsible for disease
development
There are four approaches:
1. A normal gene inserted to compensate for a
nonfunctional gene.
2. An abnormal gene treated for a normal gene
3. An abnormal gene repaired through selective
reverse mutation
4. Change the regulation of gene pairs
4. The Beginning…
• In the 1980s, Scientists began to look into
gene therapy.
– They would insert human genes into a bacteria
cell.
– Then the bacteria cell would transcribe and
translate the information into a protein
– Then they would introduce the protein into
human cells
5. The First Case
• The first gene therapy was performed on
September 14th
, 1990
– Ashanti DeSilva was treated for SCID
• Sever combined immunodeficiency
– Doctors removed her white blood cells, inserted
the missing gene into the WBC, and then put them
back into her blood stream.
– This strengthened her immune system Only
worked for a few months.
6. How It Works
• A vector delivers the therapeutic gene into a
patient’s target cell
• The target cells become infected with the viral
vector
• The vector’s genetic material is inserted into
the target cell
• Functional proteins are created from the
therapeutic gene causing the cell to return to
a normal state
7. Choices of Vectors
The ideal vector system would have the following
characteristics:
(1) an adequate carrying capacity;
(2) to be undetectable by the immune system;
(3) to be non-inflammatory.
(4) to have long duration of expression and/or the ability to
be safely re-administered.
• Viral vectors:
• Retrovirus
• Adenovirus
• Adeno-associated virus
• Herpes Simplex Virus
Non-viral vectors:
Liposome
DNA–polymer conjugates
Naked DNA
8. Viruses
• Replicate by inserting their DNA into a host
cell
• Gene therapy can use this to insert genes that
encode for a desired protein to create the
desired trait
• Four different types
9. Retroviruses
• Created double stranded DNA copies from RNA genome
– The retrovirus goes through reverse transcription using
reverse transcriptase and RNA
– the double stranded viral genome integrates into the human
genome using integrase
• integrase inserts the gene anywhere because it has no
specific site
• May cause insertional mutagenesis
– One gene disrupts another gene’s code (disrupted cell division
causes cancer from uncontrolled cell division)
– vectors used are derived from the human immunodeficiency
virus (HIV) and are being evaluated for safety
10. Adenoviruses
• Are double stranded DNA genome that cause
respiratory, intestinal, and eye infections in
humans
• The inserted DNA is not incorporate into
genome
• Not replicated though
– Has to be reinserted when more cells divide
• Ex. Common cold
11. Gene therapy using an Adenovirus vector.
A new gene is inserted into an adenovirus vector, which is used to introduce the
modified DNA into a human cell. If the treatment is successful, the new gene will
make a functional protein.
12. Adeno-associated Viruses
Adeno-associated Virus- small, single stranded DNA that insert genetic material at a
specific point on chromosome 19
From parvovirus family- causes no known disease and doesn't trigger patient immune
response.
Low information capacity
gene is always "on" so the protein is always being expressed, possibly even in instances
when it isn't needed.
hemophilia treatments, for example, a gene-carrying vector could be injected into a
muscle, prompting the muscle cells to produce Factor IX and thus prevent bleeding.
Study by Wilson and Kathy High (University of Pennsylvania), patients have not needed
Factor IX injections for more than a year
13. Non-viral Options
• Direct introduction of therapeutic DNA
– But only with certain tissue
– Requires a lot of DNA
• Creation of artificial lipid sphere with aqueous core,
liposome Carries therapeutic DNA through membrane
Chemically linking DNA to molecule that will bind to special
cell receptors
– DNA is engulfed by cell membrane
– Less effective.
14. Problems
• Delivery of DNA
• Achieving high level expression
• Maintaining stable expression
• Tissue-specific expression
• in vivo regulation
17. Ex-vivo gene therapy
Usually ex-vivo gene therapy involves the following
procedure.
1.Collect cells from an affected individual.
2.Correct the genetic defect by gene transfer into the isolated
cells.
3.Select and grow the genetically corrected cells.
4.Either infuse or transplant them back into the patient.
18. How to fix it
A
B C a beneficial geneA
virus modified virus
• A virus is found which replicates by inserting its genes into the host cell's
genome. This virus has three genes - A, B and C.
• Gene A encodes a protein which allows this virus to insert itself into the
host's genome.
• Genes B and C actually cause the disease this virus is associated with
Replace B and C with a beneficial gene. Thus, the modified virus could
introduce your 'good gene' into the host cell's genome without causing
any disease.
• So we use the modified virus to fix the “broken window”
22. In- vivo gene therapy
In vivo gene therapy entails the direct delivery of a remedial gene into the cells
Of a particular tissue of a prospective patient.
Retroviral vectors require that the target cells must be dividing in order to be
Infected.
A no. of strategies which include using viral and non-viral vector system to deliver
a therapeutic gene to cells of the target tissue, have been devised.
26. • Cystic fibrosis is a heterogeneous recessive genetic disorder with features
that reflect mutations in the cystic fibrosis transmembrane conductance
regulator (CFTR) gene.
• Cystic fibrosis was first described as a disease in the late 1930s by Dorothy
Hansine Andersen. In 1988, the first mutation for CF, ΔF508, was discovered
by Francis Collins, Lap-Chee Tsui and John R. Riordan on the 7th chromosome
of the human genome
• The mutation for CF on the 7th chromosome
• Classic cystic fibrosis is characterized by chronic bacterial infection of the
airways and sinuses, fat maldigestion due to pancreatic exocrine
insufficiency, infertility in males due to obstructive azoospermia, and
elevated concentrations of chloride in sweat.
• Patients with non classic cystic fibrosis have at least one copy of a mutant
gene that confers partial function of the CFTR protein, and such patients
usually have no overt signs of maldigestion because some pancreatic
exocrine function is preserved.
27. Hallmarks of CF
• Very salty-tasting skin
• Appetite, but poor
growth & weight gain
• Coughing, wheezing &
shortness of breath
• Lung infectionsLung infections, e.g.
pneumonia/bronchitis
28. Treatment
Gastrointestinal Treatment
• Modified diet
Due to pancreatic disorders, children with CF require a modified diet, including vitamin
supplements (vitamins A, D, E, and K) and pancreatic enzymes. Maintaining adequate
nutrition is essential. The diet calls for a high-caloric content (twice what is considered
normal for the child's age), which is typically low in fat and high in protein. Patients or
their caregivers should consult with their health care providers to determine the most
appropriate diet.
•The only way to cure CF would be to use gene therapy to replace the
defective gene or to give the patient the normal form of the protein before
symptoms cause permanent damage.
•The major goal in treating CF is to clear the abnormal and excess secretions
and control infections in the lungs, and to prevent obstruction in the intestines.
•For patients with advanced stages of the disease, a lung transplant operation
may be necessary.
•Although treating the symptoms does not cure the disease, it can greatly
improve the quality of life for most patients and has, over the years, increased
the average life span of CF patients to 30 years.
29. Gene Therapy for Cystic Fibrosis
• Cystic fibrosis should be an ideal candidate for gene
therapy, for four main reasons:
• (1) it is a single gene defect;
• (2) it is a recessive condition, with heterozygotes
being phenotypically normal (suggesting gene
dosage effects are not critical);
• (3) the main pathology is in the lung, which is
accessible for treatment;
• (4) it is a progressive disease with a virtually normal
phenotype at birth, offering a therapeutic window.
Cystic Fibrosis
30. Protein Function and Biochemistry
• CFTR controls
chloride ion
movement in
and out of the
cell.
32. • In the case of CF, gene
therapy involves inhaling a
spray that delivers normal
DNA to the lungs.
• The goal is to replace the
defective CF gene in the
lungs to cure CF or slow the
progression of the disease.
33. Problems with Gene Therapy
• Short Lived
– Hard to rapidly integrate therapeutic DNA into genome and rapidly
dividing nature of cells prevent gene therapy from long time
– Would have to have multiple rounds of therapy
• Immune Response
– new things introduced leads to immune response
– increased response when a repeat offender enters
• Viral Vectors
– patient could have toxic, immune, inflammatory response
– also may cause disease once inside
• Multigene Disorders
– Heart disease, high blood pressure, Alzheimer’s, arthritis and diabetes are
hard to treat because you need to introduce more than one gene
• May induce a tumor if integrated in a tumor suppressor gene because
insertional mutagenesis
34. References
• Molecular biotechnology principles and applications of recombinant DNA, Bernard
R.Glick and Jack J.Pasternak 2nd
edition. Page no. 560, 566.
• Burdette, Walter J. The Basis for Gene Therapy. Springfield: Charles C
Thomas,2001.
• Crayton, Stephanie. “First Clinical Trial Of Gene Therapy For Muscular Dystrophy
Now Under Way.” Medical News Today. 1 April 2006. University of North
Carolina at Chapel Hill. 11 November 2006 <www.medicalnewstoday.com>.
• Gene Therapy. Human Genome Project Information. 18 November 2005. U.S.
Department of Energy Office of Science, Office of Biological and
Environmental Research, Human Genome Program. 12 September 2006
<http://www.ornl.gov/hgmis>.
• Peel, David. “Virus Vectors & Gene Therapy: Problems,Promises & Prospects.”
Virus Vectors & Gene Therapy. 1998. Department of Microbiology &
Immunology, University of Leicester. 11 November 2006
<http://www.tulane.edu/~dmsander/WWW/335/peel/peel2.html>.
Editor's Notes
Is the most common approach
The abnormal gene would be swapped by homologous recombination
Would cause a return to normal function
Control expression of genes. Similar to epistasis, when one gene affects the expression of another gene.
A vector is a carrier molecule, usually a virus
The target cells are usually in the liver or lung