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Questions and Answers
What is the primary characteristic of the telomere loss theory of aging?
What is the primary characteristic of the telomere loss theory of aging?
According to the rate of living theory, how does metabolic rate correlate with longevity?
According to the rate of living theory, how does metabolic rate correlate with longevity?
Which theory suggests that aging is programmed and under genetic control?
Which theory suggests that aging is programmed and under genetic control?
What is a central concept of the mutation accumulation theory?
What is a central concept of the mutation accumulation theory?
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Which concept is the weak link theory most closely associated with?
Which concept is the weak link theory most closely associated with?
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Which of the following is NOT typically associated with the benefits of caloric restriction?
Which of the following is NOT typically associated with the benefits of caloric restriction?
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What is a potential negative consequence of severe caloric restriction, especially at a low BMI?
What is a potential negative consequence of severe caloric restriction, especially at a low BMI?
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Which metabolic process does intermittent fasting primarily train the body to rely on, avoiding a state of ketosis?
Which metabolic process does intermittent fasting primarily train the body to rely on, avoiding a state of ketosis?
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What is a crucial feature of the Fasting Mimicking Diet (FMD)?
What is a crucial feature of the Fasting Mimicking Diet (FMD)?
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Which phase is typically associated with therapeutic fasts exceeding 36 hours?
Which phase is typically associated with therapeutic fasts exceeding 36 hours?
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Which of the following is a noted benefit of time-restricted eating, specifically within caloric restriction?
Which of the following is a noted benefit of time-restricted eating, specifically within caloric restriction?
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What is described within the context as a potential disadvantage of time-restricted eating?
What is described within the context as a potential disadvantage of time-restricted eating?
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What effect does a progressive change from caloric restriction to increased calories have?
What effect does a progressive change from caloric restriction to increased calories have?
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Which of the following is NOT a programmable nuclease used in gene editing?
Which of the following is NOT a programmable nuclease used in gene editing?
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What is the primary mechanism by which programmable nucleases facilitate gene editing?
What is the primary mechanism by which programmable nucleases facilitate gene editing?
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Which disease has an approved gene editing therapy?
Which disease has an approved gene editing therapy?
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Which of the following is a characteristic change associated with aging?
Which of the following is a characteristic change associated with aging?
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According to the free radical theory of aging, what is the primary cause of cellular damage?
According to the free radical theory of aging, what is the primary cause of cellular damage?
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According to the mitochondrial theory of aging, which type of mutation is associated with increased lifespan?
According to the mitochondrial theory of aging, which type of mutation is associated with increased lifespan?
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Which gene mutation is associated with a shorter lifespan in studies related to the mitochondrial theory of aging?
Which gene mutation is associated with a shorter lifespan in studies related to the mitochondrial theory of aging?
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What is a key feature of aging in relation to the function of cells?
What is a key feature of aging in relation to the function of cells?
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What is a key characteristic of gene therapy medicines?
What is a key characteristic of gene therapy medicines?
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Which of the following BEST describes somatic-cell therapy?
Which of the following BEST describes somatic-cell therapy?
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What is the main purpose of isolating a gene and inserting it into a plasmid in the context of recombinant protein production?
What is the main purpose of isolating a gene and inserting it into a plasmid in the context of recombinant protein production?
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Which retroviral gene is responsible for producing the proteins that bind to the viral nucleic acids and form the structural components of the virus?
Which retroviral gene is responsible for producing the proteins that bind to the viral nucleic acids and form the structural components of the virus?
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In the production of recombinant proteins, what is the role of a plasmid?
In the production of recombinant proteins, what is the role of a plasmid?
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The LTR region in a retrovirus is formed after integration and possesses what critical activity crucial for viral replication?
The LTR region in a retrovirus is formed after integration and possesses what critical activity crucial for viral replication?
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How does Gleevec function in the treatment of Chronic Myelogenous Leukemia (CML)?
How does Gleevec function in the treatment of Chronic Myelogenous Leukemia (CML)?
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What is the main function of the Psi signal in retroviral replication?
What is the main function of the Psi signal in retroviral replication?
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What is the primary method of creating genetically-modified animals for experimental purposes?
What is the primary method of creating genetically-modified animals for experimental purposes?
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Which retrovirus is known to cause fast-developing tumors due to the expression of a viral oncogene such as src?
Which retrovirus is known to cause fast-developing tumors due to the expression of a viral oncogene such as src?
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Which of the following is NOT an example of an Advanced Therapy Medicinal Product (ATMP)?
Which of the following is NOT an example of an Advanced Therapy Medicinal Product (ATMP)?
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What is the primary mechanism by which MLV induces tumors?
What is the primary mechanism by which MLV induces tumors?
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Tissue-engineered medicines are designed to have what primary clinical outcome?
Tissue-engineered medicines are designed to have what primary clinical outcome?
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Which element in a retroviral vector is essential for the encapsidation of the therapeutic gene?
Which element in a retroviral vector is essential for the encapsidation of the therapeutic gene?
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What is the role of packaging cells in the production of retroviral vectors?
What is the role of packaging cells in the production of retroviral vectors?
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After a recombinant retroviral vector integrates into a target cell's genome, what is the main product of its expression?
After a recombinant retroviral vector integrates into a target cell's genome, what is the main product of its expression?
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Which protein is crucial for the active transfer of unspliced long transcripts in the cytoplasm within lentiviral vectors?
Which protein is crucial for the active transfer of unspliced long transcripts in the cytoplasm within lentiviral vectors?
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What is a primary safety concern regarding the use of first-generation lentiviral vectors?
What is a primary safety concern regarding the use of first-generation lentiviral vectors?
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In third-generation lentiviral vectors, what is the effect of a deletion in the 3’ LTR-SIN?
In third-generation lentiviral vectors, what is the effect of a deletion in the 3’ LTR-SIN?
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Why is it necessary to pick a promoter when using a lentiviral vector with a SIN deletion?
Why is it necessary to pick a promoter when using a lentiviral vector with a SIN deletion?
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What is a key difference in the integration characteristics of retroviral and lentiviral vectors?
What is a key difference in the integration characteristics of retroviral and lentiviral vectors?
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Which characteristic of lentiviral vectors makes them suitable for ex-vivo gene therapy?
Which characteristic of lentiviral vectors makes them suitable for ex-vivo gene therapy?
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Which components are typically included in a first-generation lentiviral vector system?
Which components are typically included in a first-generation lentiviral vector system?
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What is the function of the Rev protein in the lentiviral vector system?
What is the function of the Rev protein in the lentiviral vector system?
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What does pseudotyping in viral vectors refer to?
What does pseudotyping in viral vectors refer to?
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Why is the reduced trans-activating activity of LTR desirable in lentiviral vectors?
Why is the reduced trans-activating activity of LTR desirable in lentiviral vectors?
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Flashcards
Gene therapy medicines
Gene therapy medicines
A type of medicine that involves inserting a recombinant gene into a patient's cells to treat, prevent, or diagnose a disease.
Somatic-cell therapy medicines
Somatic-cell therapy medicines
A type of medicine that uses cells or tissues that have been modified to cure, diagnose, or prevent diseases.
Tissue-engineered medicines
Tissue-engineered medicines
A type of medicine that uses modified cells or tissues to repair, regenerate, or replace damaged human tissue.
Recombinant protein production
Recombinant protein production
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Genetically-modified plants (GMOs)
Genetically-modified plants (GMOs)
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Genetically-modified animals
Genetically-modified animals
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Gene editing
Gene editing
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Viral vectors
Viral vectors
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Telomere Loss Theory
Telomere Loss Theory
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Altered Proteins Theory
Altered Proteins Theory
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Antagonistic Pleiotropy Theory
Antagonistic Pleiotropy Theory
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Mutation Accumulation Theory
Mutation Accumulation Theory
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Rate of Living Theory
Rate of Living Theory
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Spumaretrovirinae
Spumaretrovirinae
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Genetic organization of retrovirus
Genetic organization of retrovirus
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Gag protein
Gag protein
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Pol protein
Pol protein
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Env protein
Env protein
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LTR (Long Terminal Repeat)
LTR (Long Terminal Repeat)
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Psi signal
Psi signal
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Tumorigenic retroviruses
Tumorigenic retroviruses
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Caloric Restriction (CR)
Caloric Restriction (CR)
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Protein Conservation Phase
Protein Conservation Phase
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Autophagy
Autophagy
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Time-Restricted Eating
Time-Restricted Eating
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Intermittent Fasting (16/8)
Intermittent Fasting (16/8)
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Periodic Fasting
Periodic Fasting
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Fasting Mimicking Diet (FMD)
Fasting Mimicking Diet (FMD)
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Gene Therapy
Gene Therapy
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Programmable Nucleases
Programmable Nucleases
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Meganucleases
Meganucleases
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Zinc Finger Nucleases (ZFNs)
Zinc Finger Nucleases (ZFNs)
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Transcription Activator-Like Effector Nucleases (TALENs)
Transcription Activator-Like Effector Nucleases (TALENs)
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CRISPR/Cas9
CRISPR/Cas9
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Ageing
Ageing
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Geroscience
Geroscience
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Pseudotyping
Pseudotyping
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Lentivirus
Lentivirus
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Lentiviral Vector
Lentiviral Vector
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First Generation Lentiviral Vector
First Generation Lentiviral Vector
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Second Generation Lentiviral Vector
Second Generation Lentiviral Vector
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Third Generation Lentiviral Vector
Third Generation Lentiviral Vector
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Promoter Selection for SIN Deletion
Promoter Selection for SIN Deletion
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Lentiviral vs. Retroviral Entry
Lentiviral vs. Retroviral Entry
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Integration Site Preference: Lenti vs. Retro
Integration Site Preference: Lenti vs. Retro
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Lentiviral Vector In Vivo Application
Lentiviral Vector In Vivo Application
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Study Notes
Genetic Engineering
- Advanced therapy medicinal products (ATMPs) encompass gene therapy, somatic cell therapy, and tissue-engineered medicines.
- Gene therapy involves introducing a recombinant gene to achieve therapeutic, prophylactic, or diagnostic effects.
- Somatic cell therapy modifies cells' characteristics to treat, prevent, or diagnose diseases.
- Tissue-engineered medicines repair, regenerate, or replace damaged human tissue.
Genetic Engineering Applications
- Recombinant proteins are proteins produced in cells where the gene is not naturally present. Techniques include isolating the gene, inserting it into a plasmid, using recombinant DNA to transfect a bacterium, and using the modified bacterium for protein production.
- Example: Gleevec blocks BCR-ABL kinase, preventing chronic myelogenous leukemia.
- Genetically modified organisms (GMOs) include plants and animals with altered genes to understand gene function and development.
- Gene therapy treats genetic disorders by introducing functioning genes. Types include germline therapy (permanent transfer to future generations) and somatic cell therapy (correction of deleterious effects in affected cells). Carriers of gene transfer, called vectors, are crucial. Direct uptake of oligonucleotides or plasmids is less efficient than using vectors.
Ageing, Geroscience, and Nutritional Anti-Ageing Strategies
- Ageing is defined as progressive impairment of function, making humans more vulnerable to environmental challenges and increasing disease risk.
- Ageing is associated with physiological changes like decreased regeneration, increased cross-linking, and molecule accumulation.
- Theories of ageing include free radical theory, mitochondrial theory, telomere loss theory, altered proteins, and mutation accumulation theories.
- Anti-ageing strategies, like caloric restriction and fasting, aim to reverse age-related physiological decline potentially prolonging life span.
- Some evidence suggests certain nutrients may combat ageing, though more research is required.
Gene Editing
- Gene editing is the process of precisely modifying DNA in a targeted manner, including insertions, deletions, and substitutions.
- Techniques include meganucleases, zinc-finger nucleases, transcription activator-like effector nucleases (TALENs), and CRISPR-Cas9. Each technique has varied efficacy and off-target effects.
- CRISPR-Cas9 is a gene editing tool which employs a guide RNA to target a specific DNA sequence, allowing precise DNA editing by either using NHEJ or HDR repair mechanisms. Gene editing has demonstrated success in treating genetic diseases, such as sickle cell disease.
Gene Therapy
- Various delivery methods including chemical, physical and viral exist.
- Viral vectors including Adenovirus, Adeno-associated virus, Retrovirus and Lentivirus can be engineered to deliver genes of interest to cells.
- Chemical or physical methods exist, including liposomes and proteins-DNA complexes, physical methods: electroporation and gene gun.
Anti-Ageing Therapies
- Approaches include antioxidants, resveratrol (activator of AMPK), and rapamycin/mTOR inhibitors.
- Nutritional strategies like caloric restriction and intermittent fasting are explored as potential anti-ageing interventions.
Gene Therapy for Specific Diseases
- Specific diseases like Adenosine Deaminase (ADA) deficiency and Leber's Congenital Amaurosis (LCA) have been treated with gene therapy approaches by inserting a functionnal copy of the affected gene in target cells.
- Genetic diseases, including immunodeficiencies, blood disorders, and genetic blindness have been treated by gene therapy approaches and continue to be investigated.
Cell Therapy and Regenerative Medicine
- Regenerative medicine involves using stem cells to repair or replace damaged tissues or organs.
- Adult stem cells (found in various tissues) have the ability to differentiate into specific cell types and are used in various therapies.
- iPSCs have been reprogrammed from adult cells and can develop into any cell type, providing a personalized and versatile regenerative approach.
- Strategies like transplantation of stem cells using different methods, like creating an environment for tissue healing or genetically modifying target cells, has shown positive results and are in early clinical trial stages.
Muscular Dystrophies and Haemophilia
- Muscular dystrophies are a group of genetic diseases characterized by progressive muscle weakness and degeneration.
- Haemophilia is an X-linked recessive genetic disorder causing bleeding problems.
- Therapies include exon-skipping therapies and gene and cell therapy.
Eye Diseases
- Specific eye diseases, such as Retinitis Pigmentosa (RP) and Age-related macular degeneration (AMD) have been targeted by gene therapies for treatment and prevention.
- Retinitis Pigmentosa (RP) is a group of inherited retinal diseases causing progressive vision loss often targeting photoreceptors and the retinal pigmented epithelium (RPE).
- Age-related macular degeneration (AMD) causes degeneration of the macula in the retina, critical for central vision and is associated with an increase in vessel permeability and blood leakage (angiogenesis and neovascularisation).
Neurological System Diseases and Therapies
- Neurological diseases, such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (ALS), are characterised by progressive neuronal degeneration.
- Therapies for these diseases include replacement therapy, deep brain stimulation, and cell/gene therapy approaches (though less successful for effective treatment).
Cardiovascular System Diseases and Therapies
- Cardiovascular diseases (CVDs) are a group of conditions affecting the heart and blood vessels. Common causes include obstruction of blood vessels due to plaques or fatty deposits.
- Therapies involve improving blood flow (e.g., angioplasty with stent placement) and strategies like neoangiogenesis (development of new vessels), cardioprotection (salvaging/preventing further degeneration), and cardiac regeneration.
Cancer
- Specific gene therapies targeting oncogenes and developing oncolytic viruses also exist for specific cancers.
- Oncolytic viruses are viruses that selectively replicate and kill tumour cells, exploiting the unique metabolic/genetic characteristics of these cells.
- Strategies include increasing antigenic stimulation or eliciting an enhanced cytotoxic T-cell response to target cancer cells.
Gene Editing
- Programmable nucleases and repair mechanisms (such as ZFNs, TALENs, and CRISPR-Cas9) are methods for targeted genetic alterations.
- Types of editing include inducing Double Strand Breaks (DSBs) for knockouts or homology directed repair (HDR) for targeted edits. Repair mechanisms such as Non-Homologous End Joining (NHEJ) and HDR can lead to varied outcomes based on the situation.
RNA Therapies
- Applications: infectious diseases, cancer immunotherapies, protein replacement, and genome engineering.
- RNA therapeutic approaches utilize modifications of RNA molecules for specific targeting of genetic or biological processes.
Overview of Various Therapies
- Gene editing is a powerful therapeutic tool for treating various diseases, although ethical considerations and practical limitations still need addressing.
- RNA therapeutics are used for specific indication, and off-target effects and duration of the treatment need to be rigorously controlled.
- Cell therapies using stem cells are targeted for tissue repair, and regeneration (such as cardiac regeneration).
- Regenerative approaches and engineered tissue transplantation may prove useful in treating numerous conditions.
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Description
This quiz explores the fundamentals of genetic engineering, including advanced therapy medicinal products like gene therapy, somatic cell therapy, and tissue-engineered medicines. It will also cover applications such as recombinant proteins and genetically modified organisms, providing insights into modern therapeutic strategies and their implications.