Nucleic acid based Drug delivery system is one of the trending research area, which i have taken and made as Powerpoint for easy and quick learning purpose
Computational modelling of drug disposition lalitajoshi9
computational modelling of drug disposition is the integral part of computer aided drug design. different kinds of tools being used in the prediction of drug disposition in human body. This topic in the CADD explains the details about the drug disposition, active transporters and tools.
REGULATORY AND INDUSTRY VIEWS ON QbD, SCIENTIFICALLY BASED QbD- EXAMPLES OF A...Ardra Krishna
The pharmaceutical Quantity by Design (QbD) is a systemic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quantity risk management.
QbD has been adopted by U.S Food and Drug Administration (FDA) for the discovery, development and manufacture of drugs.
Quality- by- design (QbD) is a concept introduces by the International Conference on Harmonization (ICH) Q8 guidelines.
Statistical modeling in pharmaceutical research and developmentPV. Viji
Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
This will provide you the introduction about the tumor, its Anatomy & Physiology,How they are monitored?, Classification and grades of tumor, Tumor Targeting Techniques, strategies and Principles. Also provide you some examples of Marketed products.
Definition, Gene therapy, types of gene therapy, germline gene therapy, somatic cell gene therapy, basic process of gene therapy and potential targets for gene therapy.
Computational modelling of drug disposition lalitajoshi9
computational modelling of drug disposition is the integral part of computer aided drug design. different kinds of tools being used in the prediction of drug disposition in human body. This topic in the CADD explains the details about the drug disposition, active transporters and tools.
REGULATORY AND INDUSTRY VIEWS ON QbD, SCIENTIFICALLY BASED QbD- EXAMPLES OF A...Ardra Krishna
The pharmaceutical Quantity by Design (QbD) is a systemic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quantity risk management.
QbD has been adopted by U.S Food and Drug Administration (FDA) for the discovery, development and manufacture of drugs.
Quality- by- design (QbD) is a concept introduces by the International Conference on Harmonization (ICH) Q8 guidelines.
Statistical modeling in pharmaceutical research and developmentPV. Viji
Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
This will provide you the introduction about the tumor, its Anatomy & Physiology,How they are monitored?, Classification and grades of tumor, Tumor Targeting Techniques, strategies and Principles. Also provide you some examples of Marketed products.
Definition, Gene therapy, types of gene therapy, germline gene therapy, somatic cell gene therapy, basic process of gene therapy and potential targets for gene therapy.
Gene therapy is emerging branch of healthcare, we can see that with the possible development it has potential to treat multiple genetic as well as other conditions and disease
hope young scholar can find this presentation useful and i am open to any suggestions
Nucleic Acid Based Therapeutic Delivery System.pptxRAHUL PAL
Therapeutic nucleic acids (TNAs) are nucleic acids themselves or closely related compounds used to treat disease. Although various types of TNAs exist, they share a common mechanism of action that is mediated by sequence‐specific recognition of endogenous nucleic acids through Watson–Crick base pairing 7.
What are the advantages of nucleic acid based therapeutics?
The major advantage of nucleic acid-based therapeutics lies in the fact that they can be used to accurately target a tumor or tissue, then have a specific therapeutic protein, biologic, or immune engager expressed only at the site of interest.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Nucleic acid based therapeutic drug delivery system
1. NUCLEIC ACID BASED
THERAPEUTIC DELIVERY
SYSTEM
SUBMITTED BY:
T. SRI TEJA
M. PHARMACY
DEPARTMENT OF PHARMACEUTICS
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3. Introduction
• The delivery of nucleic acid molecules into cells to alter physiological functions at the
genetic level is a powerful approach to treat a wide range of inherited and acquired
disorders
• This technique has been a common research tool in the laboratory for decades to study
gene functions.
• The therapeutic potential of this approach was not fully realized due to lack of reliable
and practical methods to transfer and express recombinant DNA in mammalian cells
• By the 1980s, a series of clinical trials demonstrated therapeutic efficacy from the
transplantation of virally transduced cell.
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4. GENE THERAPY
• Insertion of new genetic material into the cells of an individual with the intention of
producing a therapeutic benefit for the patient is human gene therapy.
• Gene therapy quickly became an intensely investigated field with the promising
potential to devise treatment not only for genetic diseases but also for a wide range of
disorders including metabolic disorders, infectious diseases, chronic illnesses and
cancer.
• The power of gene therapy is derived from the ability to manipulate cell physiology at
genetic and epigenetic levels.
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6. Germ line Gene therapy
• In Germ line gene therapy(GGT) germ cells are modified by introduction of
therapeutic genes.
• Modifying a germ cell causes all the organism's cells to contain the modified
gene.
• The change is therefore heritable and passed on to later generations.
• For safety, ethical and technical reasons, it is not being attempted at present.
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8. Somatic Cell Gene Therapy
• In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into
any cell other than a germ cell.
• Introduction of genes into bone marrow cells, blood cells, skin cells.
• It will not be inherited to later generations.
• Most focus on severe genetic disorders, including immuno deficiencies,
hemophilia, thalassaemia, and cystic fibrosis. such single gene disorders are good
candidates for somatic cell therapy.
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10. Types of Somatic Cell Gene Therapy
Ex Vivo
Can be applied to
only selected tissues
Cells are modified
outside the body and
transplanted back
In Vivo
The direct delivery of
the therapeutic gene
into the target cells
Cells are modified
inside the body and
transplanted back
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12. In Vivo Gene Therapy
• Direct delivery of therapeutic gene into target cell into patients body.
• Carried out by viral or non viral vector systems.
• It can be the only possible option in patients where individual cells cannot be
cultured in vitro in sufficient numbers (e.g. brain cells).
• In vivo gene transfer is necessary when cultured cells cannot be re-implanted in
patients effectively.
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15. Process of Gene Therapy
• A Gene that is inserted directly into a cell usually does not function. instead, a
carrier called a vector is genetically engineered to deliver the gene.
• Viruses are often used as vectors because they can deliver the new gene by
infecting the cell.
• Delivery of gene into cells can also be accomplished by some other methods like
DNA complexes etc.
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16. 5/19/2019Vignan Pharmacy college, Vadlamudi, Guntur 16
Gene Therapy
Viral Vector Non Viral Vector
Adenovirus vector
system for treating
common cold
Synthetic vector based
delivery for treatment of
cancer
17. VIRAL VECTOR
• Viruses have evolved a way of encapsulating and delivering their genes to human
cells in a pathogenic way by manipulating the viral genome to remove disease
causing gene and inserting therapeutic one.
• Viruses bind to their hosts and introduce their genetic material into the host cell.
• Viruses used are altered to make them safe, although some risks still exist with
this type of gene therapy.
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19. TYPES OF VIRAL VECTORS
1. Retrovirus vector system: Recombinant retrovirus have the ability to integrate
into the host genome in a stable fashion.
2. Adeno virus vector system: Adeno virus with DNA genome is a good carrier.
Useful in treating common cold.
3. Adeno associated virus vector: It is a single stranded, non pathologic small
DNA virus. It can integrate into Chromosome 19.
4. Herpes simplex virus vector: They persist into nervous cell. These viruses
have natural tendency to infect particular type of cell
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20. • The non-viral vectors are naked DNA, particle based and chemical based.
• They are administered by direct administration (plasmid dna/naked dna)/
chemical /physical.
• Most of cardiovascular clinical trials use non-viral vectors as a mode of gene
transfer.
• Non-viral vectors are generally used to transfer following types of nucleic acids
1. Small DNA
2. Large DNA
3. RNA
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NON VIRAL VECTOR
22. • Needle Injection: The genetic material of interest is administered through a
needle carrying syringe into tissue or systemic injection from a vessel. Without
any carrier it is the simplest and safest method of gene transfer. The efficiency is
low due to rapid degradation by nucleases in serum.
• Electroporation: The other terms used for electroporation are gene electro
injection, gene electro transfer. applying an electric field that is greater than the
membrane capacitance will cause charges of opposite polarity to line up on either
side of cell membrane thus forming a potential difference at a specific point on
the cell surface. As a result membrane breakdown form a pore and allows the
molecule to pass. Pore formation occurs in approximately 10 nanoseconds.
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PHYSICAL METHODS
23. • GENE GUN: Employs a high pressure delivery system to shoot tissue with gold
or tungsten particles that are coated with DNA
• HYDROPORATION: It is also called as hydrodynamic gene transfer. The
technique uses hydrodynamic pressure to penetrate the cell membrane.
Hydrodynamic pressure is created by injecting large volume of DNA solution in
a fraction of time. This creates increased permeability of capillary endothelium
and forms pores in plasma membrane encircling parenchyma cells. The
therapeutic gene of interest can reach the cell through these pores and these
membrane pores are closed later thus keeping the genetic material inside the cell.
This technique is most commonly used for gene therapy research in hepatic cells.
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26. GENE THERAPY FOR TREATMENT OF GENETIC DISORDERS
• Genetic disorders are illnesses stemming from errors in a person’s genes
• Any mistake in a gene can alter how a specific protein is produced
• Without proper proteins, the body will not function properly and will take on a
chronic and possibly life threatening condition
• Genetic disorders can be congenital meaning they occur from birth or they may
develop over time
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27. GENE THERAPY CURES BLINDNESS
• Cures blindness of inherited condition
• Inherited blindness caused by an abnormality in a gene called RPE65
• The condition appears at birth or in the first few months of life and causes
progressive worse and loss of vision.
• It can be treated by enabling access to cells beneath the retina of patients.
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28. GENE THERAPY FOR CANCER TREATMENT
ONCOGENE ACTIVATION:
- Done by using antisense therapy
- Reduces the expression of antigenic proteins responsible for malignancies
VIRUS MEDIATED ONCOLYSIS:
- Adeno virus and herpes virus can infect and cause lysis of cancer cells.
AUGMENTATION OF TUMOR SUPRESSOR GENE:
- It is done by repair of tumor suppressor gene in malignant cells.
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29. GENE THERAPY IN SOME OTHER DISEASES
• GENE THERAPY CAN ALSO USED IN OTHER DISEASES LIKE
- Diabetes
- Cystic fibrosis
- Parkinson's Disease
- X-SCID (X- Linked severe combined immunodeficiency)
- Adenosine deaminase deficiency
- Muscular dystrophy
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30. LIMITATIONS OF GENE THERAPY
• Immune hyper responsiveness directed against viral vector components may
leads to deactivation of gene
• Virus that used as vectors may also cause diseases inside the body.
• Once we does not have control over the site of insertion of genome
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31. CONCLUSION
• Nucleic acid based therapeutic delivery is a technique that will be very useful for
the treatment of many diseases.
• Gene therapy can be helpful in many genetic diseases which can prevent those
diseases for future generations.
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32. REFERENCES
• S.P . Vyas and Khar; Controlled and targeted drug delivery system; 2nd edition;
Page. No: 520-560
• Charlie Yu Ming Hsu and Hasan Iludag; Nucleic Acid based gene therapeutics:
Delivery challenges and modular design of nonviral gene carriers and expression
cassettes to overcome intracellular barriers for sustained targeted expression;
Journal of Drug targeting; Page No-301-319; 2012; 20(4)
• https://en.wikipedia.org/w/index.php?title=Gene_therapy&oldid=886560975
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