UPSC MainsZOOLOGY-PAPER-I202215 Marks
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Q29.

What is gene therapy? Citing suitable examples explain germline and types of somatic cell gene therapy.

How to Approach

This question requires a detailed understanding of gene therapy, differentiating between germline and somatic cell therapy, and providing specific examples. The answer should begin with a clear definition of gene therapy. Then, a comparative analysis of germline and somatic cell therapy, highlighting their differences in target cells, heritability, and ethical concerns, is crucial. Finally, examples of each type should be provided to illustrate the concepts. A structured approach using headings and subheadings will enhance clarity.

Model Answer

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Introduction

Gene therapy, a revolutionary field in medicine, involves altering an individual’s genes to treat or prevent disease. It holds immense promise for treating genetic disorders, cancers, and infectious diseases. While still evolving, gene therapy has witnessed significant advancements in recent decades, with several therapies now approved for clinical use. The core principle revolves around introducing genetic material into cells to compensate for abnormal genes or to make cells better at fighting disease. This can be achieved through various vectors, most commonly viruses, to deliver the therapeutic gene. Understanding the distinction between germline and somatic cell gene therapy is fundamental to grasping the ethical and practical implications of this technology.

What is Gene Therapy?

Gene therapy is a technique that uses genes to treat or prevent disease. It involves introducing genetic material into cells to compensate for abnormal genes or to make cells better at fighting disease. The genetic material can be delivered using various methods, including viral vectors, plasmids, and nanoparticles. The goal is to correct the underlying genetic defect causing the disease or to enhance the body’s ability to fight it.

Germline Gene Therapy

Germline gene therapy involves modifying the genes in gametes (sperm or egg cells) or early embryos. This means that the changes made will be heritable and passed down to future generations. Because of the potential for unforeseen consequences and ethical concerns, germline gene therapy is currently not permitted in most countries, including the United States and many European nations.

Characteristics of Germline Gene Therapy:

  • Target Cells: Gametes (sperm and egg) or early embryos.
  • Heritability: Changes are passed on to future generations.
  • Ethical Concerns: Significant ethical concerns regarding unintended consequences, altering the human gene pool, and potential for misuse.
  • Current Status: Largely prohibited due to ethical and safety concerns.

Example: While not currently practiced, a hypothetical example would be correcting the gene responsible for cystic fibrosis in a sperm cell, ensuring that any offspring would not inherit the disease. This remains largely theoretical due to ethical constraints.

Somatic Cell Gene Therapy

Somatic cell gene therapy involves modifying the genes in somatic cells (any cell in the body that is not a gamete). These changes are not heritable and are limited to the individual receiving the therapy. Somatic cell gene therapy is the more commonly practiced form of gene therapy and has shown promising results in treating various diseases.

Types of Somatic Cell Gene Therapy:

  • Gene Augmentation Therapy: This involves adding a functional copy of a gene to compensate for a non-functional gene. This is often used for recessive genetic disorders.
  • Gene Inhibition Therapy: This involves blocking the expression of a gene that is causing harm. This can be used for dominant genetic disorders or cancers.
  • Gene Editing: This involves using tools like CRISPR-Cas9 to precisely edit the genome, correcting mutations or inserting new genes.

Examples of Somatic Cell Gene Therapy:

  1. Severe Combined Immunodeficiency (SCID-X1): In 2000, a clinical trial used retroviral vectors to deliver a functional copy of the IL2RG gene into the bone marrow cells of children with SCID-X1 (also known as “bubble boy disease”). While some patients developed leukemia as a side effect, the therapy successfully restored immune function in others.
  2. Spinal Muscular Atrophy (SMA): Zolgensma (onasemnogene abeparvovec-xioi) is a gene therapy approved by the FDA in 2019 for treating SMA, a genetic disorder that affects motor neurons. It uses an adeno-associated virus (AAV) vector to deliver a functional copy of the SMN1 gene.
  3. Leber’s Congenital Amaurosis (LCA): Luxturna (voretigene neparvovec-rzyl) is an AAV-based gene therapy approved in 2017 for treating LCA, a rare inherited retinal disease. It delivers a functional copy of the RPE65 gene to retinal cells, improving vision.
Feature Germline Gene Therapy Somatic Cell Gene Therapy
Target Cells Gametes or early embryos Somatic cells
Heritability Changes are heritable Changes are not heritable
Ethical Concerns High – altering the human gene pool Lower – limited to the individual
Current Status Largely prohibited Clinically practiced

Conclusion

Gene therapy represents a significant advancement in medical science, offering potential cures for previously untreatable genetic diseases. While germline gene therapy remains ethically contentious and largely prohibited, somatic cell gene therapy is becoming increasingly refined and effective, as evidenced by the approvals of therapies like Zolgensma and Luxturna. Continued research and development, coupled with careful ethical considerations, will be crucial to unlocking the full potential of gene therapy and ensuring its safe and responsible application for the benefit of humanity.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Vector
A vector is a vehicle used to deliver genetic material into cells. Common vectors include viruses (e.g., retroviruses, adenoviruses, AAVs) and plasmids.
CRISPR-Cas9
CRISPR-Cas9 is a revolutionary gene editing technology that allows scientists to precisely target and modify DNA sequences within cells. It has significantly advanced the field of gene therapy by enabling more accurate and efficient gene editing.

Key Statistics

As of 2023, over 2,500 gene therapy clinical trials have been conducted worldwide, with more than 40 gene therapies approved for use in various countries.

Source: Alliance for Regenerative Medicine (ARM), 2023

The global gene therapy market was valued at USD 4.8 billion in 2022 and is projected to reach USD 35.2 billion by 2032, growing at a CAGR of 22.5% from 2023 to 2032.

Source: Global Market Insights, 2023

Examples

Beta-Thalassemia Treatment

Researchers are exploring gene therapy for beta-thalassemia, a blood disorder, by introducing a modified beta-globin gene into the patient’s hematopoietic stem cells. Early clinical trials have shown promising results in reducing or eliminating the need for blood transfusions.

Frequently Asked Questions

What are the risks associated with gene therapy?

Risks include immune responses to the vector, off-target effects (where the gene is inserted into the wrong location in the genome), and the potential for insertional mutagenesis (causing cancer). These risks are being actively addressed through ongoing research and improved vector design.

Topics Covered

BiotechnologyMedicineBiologyGene TherapyGermline TherapySomatic Cell Therapy