In a world-first, US researchers successfully used CRISPR-based gene editing to treat a baby named KJ with CPS-1 deficiency, a life-threatening genetic disorder.

About CPS-1 Deficiency

• Carbamoyl Phosphate Synthetase 1 (CPS-1) deficiency is a rare urea cycle disorder that impairs the liver’s ability to eliminate ammonia, with nearly 50% infant mortality.
• Symptoms: The following signs are seen in patients namely:  lethargy and respiratory distress due to ammonia build-up in the body.
• Limitations of Conventional Treatment: Liver transplant is often the only long-term treatment, but infants typically aren’t ready for the procedure early in life.
• Therapeutic Breakthrough: Doctors used customised CRISPR-based gene-editing therapy called “k-abe” to correct the mutation in KJ’s genome.
• Targeted Delivery: The gene-editing tool was encapsulated in lipid nanoparticles for safe delivery to the liver.
• Outcomes: After three infusions, the baby could tolerate protein, needed lower medication doses, and began gaining weight without showing any severe side effects.
• FDA Approval: The U.S. FDA granted emergency approval for this personalized therapy, highlighting the growing acceptance of gene-editing in rare disease management.

Significance of the Success

• Clinical success of In-vivo Editing : This was the first individualized in-vivo gene-editing treatment conducted directly inside a human body.
• Customised Therapy: It paves the way for targeted treatments of thousands of rare genetic diseases where organ transplant or lifelong drug use are currently the only options.
• Precise Treatment: The use of lipid nanoparticles ensured safe and precise delivery to the liver without triggering immune complications.

What is Gene Editing Therapy?

• Gene editing therapy is a form of treatment where DNA is altered to correct defective genes responsible for disease development.
• It differs from gene therapy, which generally adds a normal gene without altering the existing one.
• Tool Used: The most common tool is CRISPR-Cas9, which acts as molecular scissors to cut and replace faulty DNA sequences.

Types of Gene Therapy

Types based on Cell Targeted

Types Based on site of  Procedure: In-Vivo and Ex-Vivo Therapy

Applications

• Current Use: Treatment for sickle cell anemia, cystic fibrosis, hemophilia, leukemia, and now CPS-1 deficiency.

• Potential Use: Could treat diseases like Alzheimer’s, Parkinson’s, heart disease, and other metabolic or neurodegenerative disorders.
• Emerging Use: In cancer immunotherapy, where edited cells target and kill tumor cells.

Ethical and Regulatory Roadblocks

• Ethical Concerns: Gene editing poses risks of unintended genetic mutations, long-term health consequences, and controversies around germline modifications that affect future generations.
  • Informed consent becomes complex, especially in infants.
• Chances of Misuse: There’s growing fear around the potential misuse of technology for non-therapeutic enhancements, such as creating “designer babies” with selected traits, raising socio-ethical and justice concerns.
• Regulatory Oversight: The field demands strict regulatory frameworks to ensure safety, efficacy, and accountability, especially when used in vulnerable populations like newborns.
• Global Divergence: While nations like the US and China lead in trials and approvals, many countries remain cautious, citing lack of long-term safety data and unresolved ethical questions.
• Cost and Accessibility: Gene therapies are highly expensive, limiting access to affluent populations and widening healthcare inequality. Ensuring affordability remains a significant policy challenge.

Conclusion

The success of gene-editing therapy in saving an infant with CPS-1 deficiency marks a transformative leap in precision medicine. With ethical caution and regulatory clarity, such personalized genomic interventions can revolutionize the future of healthcare, including in countries like India.