UPSC CSE Prelims
Gene Therapy and CRISPR Previous Year Questions (PYQs)

Detailed Explanation:

Statement 1 — Correct. Genetic medicines (gene therapy and gene editing) treat diseases at their root cause by introducing, removing, or changing genetic material to correct or compensate for faulty/missing genes responsible for a disease.

Statement 2 — Correct. Genetic material cannot be injected directly — it requires a vector (carrier):

Statement 3 — Incorrect. Genetic medicines do NOT alter the entire DNA sequence. The human genome has ~3 billion base pairs and 20,000+ genes. Gene therapies are highly precise — targeting only specific localized sequences or single genes while leaving the vast majority of native DNA completely unchanged.

Key Trick: Statement 3 uses the word "entire" — a classic UPSC exaggeration trap. Precision, not wholesale alteration, is the hallmark of genetic medicine.

Detailed Explanation:

Answer: Option 4 — 1, 2 and 3

All three statements regarding genome editing and stem cell technologies are scientifically correct and represent current capabilities in biotechnology.

✅ Statement 1 – Correct: Germline gene editing using technologies like CRISPR-Cas9 can introduce genetic changes in germ cells (eggs or sperm), making these modifications heritable and transmissible to future generations.

✅ Statement 2 – Correct: Genome editing can be performed at the early embryonic stage (zygote or blastocyst stage) before birth, allowing for correction of genetic mutations that cause hereditary diseases.

✅ Statement 3 – Correct: Human induced pluripotent stem cells (hiPSCs) can be injected into pig embryos to create human-animal chimeras, a technique used in research for studying organ development and exploring potential for human organ transplantation.

📝 Short Notes: Genome Editing and Stem Cell Technologies

• CRISPR-Cas9: A revolutionary gene-editing tool that allows precise modifications to DNA sequences in living organisms, enabling targeted correction of genetic defects.
• Germline Editing: Modifications made to germ cells (eggs, sperm) or early embryos that are heritable and passed to future generations, raising significant ethical concerns.
• Somatic Gene Editing: Changes made to non-reproductive cells that affect only the individual and are not passed to offspring.
• Induced Pluripotent Stem Cells (iPSCs): Adult cells reprogrammed to an embryonic-like pluripotent state, capable of differentiating into any cell type in the body.
• Chimeras: Organisms containing cells from two different species; human-animal chimeras are used in research to study disease mechanisms and organ development.
• Ethical Concerns: Germline editing and chimera research raise questions about human dignity, unintended consequences, equity in access, and the creation of designer babies.
• Regulatory Status: Many countries have banned or strictly regulate germline editing in humans, though research continues in controlled settings for therapeutic purposes.

Detailed Explanation:

Answer: Option 1 — 1, 2 and 4

RNA interference (RNAi) is a biological process where RNA molecules inhibit gene expression by neutralizing targeted mRNA molecules. This technology has gained popularity for its applications in gene silencing therapies, cancer treatment, and developing disease-resistant crops.

✅ Statement 1 – Correct: RNAi technology is extensively used in developing gene silencing therapies by targeting and reducing specific gene expressions to treat various diseases.
✅ Statement 2 – Correct: RNAi-based therapies are being actively researched and developed for cancer treatment by silencing genes responsible for tumor growth and proliferation.
❌ Statement 3 – Incorrect: RNAi is not used for hormone replacement therapies; it works by silencing genes rather than introducing hormones into the body.
✅ Statement 4 – Correct: RNAi technology is successfully applied in agriculture to produce crop plants resistant to viral pathogens by targeting and degrading viral RNA.

📝 Short Notes: RNA Interference (RNAi) Technology

• Definition: RNAi is a natural cellular process where double-stranded RNA molecules trigger the degradation of specific mRNA, thereby silencing gene expression.
• Discovery: First discovered in the 1990s by Andrew Fire and Craig Mello, who won the Nobel Prize in 2006 for their work.
• Mechanism: Small interfering RNAs (siRNAs) or micro RNAs (miRNAs) bind to complementary mRNA sequences, leading to their degradation or translational repression.
• Medical Applications: Used in treating genetic disorders, viral infections, and cancer by silencing disease-causing genes; several RNAi-based drugs are in clinical trials or approved.
• Agricultural Applications: Development of virus-resistant crops, enhanced nutritional content, and improved stress tolerance in plants.
• Limitations: Off-target effects, delivery challenges to specific tissues, and potential immune responses remain areas of ongoing research.

Detailed Explanation:

Answer: Option 1 — A molecular scissors used in targeted gene editing

Cas9 is an RNA-guided endonuclease enzyme that functions as molecular scissors, capable of cutting DNA at precise locations within a genome. It is the key component of the CRISPR-Cas9 gene editing system, which has revolutionized genetic engineering by enabling targeted modifications to DNA sequences in living organisms.

📝 Short Notes: CRISPR-Cas9 Gene Editing Technology

• CRISPR-Cas9 stands for Clustered Regularly Interspaced Short Palindromic Repeats associated with Cas9 protein.
• Mechanism: The system uses a guide RNA (gRNA) to direct the Cas9 enzyme to a specific DNA sequence, where it makes a precise cut.
• Function: After cutting, the cell's natural DNA repair mechanisms can be harnessed to add, delete, or replace genetic material at the targeted location.
• Applications: Treatment of genetic diseases, development of disease-resistant crops, creation of genetically modified organisms, and basic research in genomics.
• Advantages: More precise, efficient, and cost-effective compared to earlier gene editing technologies like zinc finger nucleases and TALENs.
• Nobel Prize 2020: Emmanuelle Charpentier and Jennifer Doudna were awarded the Nobel Prize in Chemistry for developing CRISPR-Cas9 gene editing.
• Ethical Concerns: Potential misuse in human germline editing, unintended off-target effects, and ecological impacts of genetically modified organisms.

Detailed Explanation:

Answer: Option 3 — Reproductive cloning of animals

Somatic Cell Nuclear Transfer (SCNT) is a cloning technique where the nucleus of a somatic (body) cell from a donor organism is transferred into an enucleated egg cell (an egg whose nucleus has been removed). The reconstructed egg is then stimulated to divide and develop into an embryo, which is implanted into a surrogate mother to produce a genetically identical clone of the donor organism. This process is called reproductive cloning.

Famous example: Dolly the sheep (1996) was the first mammal successfully cloned using SCNT technology. This technology has applications in livestock breeding, conservation of endangered species, and biomedical research. However, it is not related to biolarvicides, biodegradable plastics, or producing disease-free organisms through this specific mechanism.