Mains Practice Questions

Introduction:

• Within a decade of its discovery, CRISPR-Cas9 technology has progressed from a laboratory genome-editing tool to a clinically approved therapy for genetic disorders such as sickle cell disease.
• The approval of treatments like Casgevy marks a transformative moment in modern medicine, demonstrating how precise gene editing can correct or bypass disease-causing mutations at their biological root.

Body:

Scientific Mechanism of CRISPR-Based Therapy

• CRISPR-Cas9 acts as a precise pair of "molecular scissors" that allows scientists to locate and edit specific strands of DNA within a living cell.
  • Target Identification (The Guide): Scientists design a synthetic Guide RNA (gRNA) that specifically matches the DNA sequence of the defective gene they want to fix.
  • Precision Cutting (The Scissors): The gRNA directs the Cas9 enzyme (molecular scissors) to the exact spot on the DNA strand, where Cas9 acts to cut both strands of the DNA.
  • Cellular Repair Activation: The cell detects this break and immediately activates its natural DNA repair mechanisms (such as Non-Homologous End Joining or Homology-Directed Repair) to fix the cut.
  • Gene Correction: During this repair process, the cell either disables the bad gene (knock-out) or incorporates a healthy DNA template provided by scientists (knock-in), permanently correcting the genetic error.

Evaluation of Effectiveness Based on Global Clinical Outcomes

• Hematology- "Functional Cure" Achieved : CRISPR-based therapy, particularly Casgevy (exa-cel), has shown remarkable therapeutic success in both Sickle Cell Disease (SCD) and transfusion-dependent β-thalassemia (TDT).
  • In SCD trials, over 90% of treated patients achieved complete elimination of vaso-occlusive crises (VOCs).
• Cardiovascular Disease: Promising but Safety-Watch:
  • Cholesterol (VERVE-101): Demonstrated the ability to lower LDL-C (bad cholesterol).
  • Outcomes: While effective at lowering cholesterol, trials have faced scrutiny regarding safety signals (adverse events in high-risk heart patients).

Limitations and Concerns

• Off-target effects: Unintended edits remain a concern for long-term safety.
• Delivery barriers: Efficient delivery to organs like the brain and heart is still limited.
• Immune reactions: Cas proteins can trigger immune responses.
• Ethical concerns: Fear of germline editing and “designer babies.

Future Pathway for CRISPR-Cas9 technology

• Strengthen safety frameworks through long-term monitoring, global ethical guidelines, and stricter assessment of off-target effects.
• Improve delivery technologies such as advanced viral vectors and lipid nanoparticles for efficient, organ-specific gene editing.
• Enhance affordability and accessibility by promoting public–private partnerships, tiered pricing, and domestic manufacturing capacity.
• Invest in research for complex diseases to expand CRISPR applications beyond monogenic disorders to cancers, neurodegenerative and metabolic diseases.

Conclusion:

While CRISPR therapies have opened a new frontier of “single-shot cures,” realizing their full public-health impact will require parallel advances in safer conditioning methods, cost reduction, and equitable global delivery systems.