First-Ever Personalized Gene-Editing Therapy

GS3 – Science & Tech

 

Context:

In a landmark development, scientists in the United States have successfully trialled a custom gene-editing treatment to help an infant suffering from carbamoyl phosphate synthetase 1 (CPS-1) deficiency.

This innovative therapy, designed specifically for that child, used a CRISPR-based technique tailored to the individual’s genetic mutation. Unlike earlier CRISPR approaches, which required modification of stem cells outside the body, this therapy was administered directly into the infant’s liver. It involved the use of lipid nanoparticles loaded with RNA and a guide sequence to target the faulty gene.

About CPS-1 Deficiency

CPS-1 deficiency is a rare inherited metabolic condition that disrupts the body’s urea cycle—the main pathway responsible for eliminating excess nitrogen (in the form of ammonia) from the body.

• Urea Cycle Function: Normally, ammonia generated during protein breakdown is converted into urea and excreted through urine. The CPS-1 enzyme, found in the mitochondria of liver cells, initiates this process.
• Impact of Deficiency: In the absence or malfunction of this enzyme, ammonia accumulates in the blood, leading to hyperammonemia, a condition that can be toxic and potentially life-threatening.

Understanding Gene Editing

Gene editing refers to precise techniques used to modify the DNA of living organisms, including humans, plants, and microbes.

• Function: Scientists can add, remove, or modify genetic material at exact locations in the genome.
• Tools:
  • CRISPR-Cas9: A widely-used tool that acts like molecular scissors to cut DNA at specific locations.
  • Other techniques: TALENs and Zinc Finger Nucleases (ZFNs) are alternative methods.

Modes of Gene Editing

Somatic Gene Editing	Germline Gene Editing
Alters non-reproductive body cells (like liver, skin, or blood).	Targets reproductive cells (sperm, egg) or early embryos.
Aimed at treating diseases within the individual.	Changes are passed on to offspring.
Non-heritable modifications.	Heritable changes that affect future generations.
Example: Gene therapy for sickle cell anaemia.	Example: Preventing inherited disorders at the embryonic stage.

Applications of Gene Editing

• Medical Advancements: Treating or curing genetic diseases like cystic fibrosis, sickle cell anaemia, and certain cancers.
• Personalised Therapies: Developing treatments based on an individual’s unique genetic profile.
• Agriculture: Creating crops with better yields, pest resistance, and adaptability to climate change.
• Genetic Disease Prevention: Especially through germline editing to eliminate hereditary disorders before birth.

Concerns & Ethical Challenges

• Safety Issues: Potential for unintended or off-target mutations that might cause harm.
• Moral Dilemmas: Especially in germline editing—concerns about consent, identity, and the possibility of engineered traits in babies.
• Uncertain Outcomes: Long-term effects on humans and the environment remain largely unknown.
• Social Inequity: Risk of these advanced therapies being accessible only to wealthy populations, increasing inequality.

Recommended Actions

• Boost R&D: Focus on refining CRISPR and newer technologies like base and prime editing to improve accuracy and safety.
• Build Strong Regulations: Formulate comprehensive, globally coordinated policies to ensure responsible use.
• Prioritise Ethics: Maintain strict oversight to prevent misuse, especially in non-therapeutic genetic enhancements.
• Promote Inclusivity: Ensure that advancements in gene therapy are affordable and accessible to all sections of society, especially underprivileged communities.