Single Genome-Editing Strategy for Multiple Genetic Disorders

Why in News?

Recently, a study published in Nature reported a new genome-editing strategy (PERT) that can potentially treat multiple genetic disorders caused by nonsense mutations.

• Genes – They are made of DNA (deoxyribonucleic acid).
  • It contains instructions for cell functioning and the characteristics that make a person unique.

Genetic disorders occur when a mutation (a harmful change to a gene, also known as a pathogenic variant) affects an individual’s genes. It disrupts the cell’s ability to build a complete, functional protein.

• Genome editing – Technologies that give scientists the ability to change an organism's DNA.
• It allows genetic material to be added, removed, or altered at particular locations in the genome.
• It is also called gene editing. And the best example is CRISPR-Cas9.
• Background – A nonsense mutation is a type of genetic mutation where a wrong DNA letter changes a normal codon into a “stop” codon.
  • A codon is a group of 3 DNA/RNA letters that tells the cell which amino acid to add to a protein.
• Nonsense mutations account for about one-fourth of all known disease-causing genetic changes.
  • As it stops protein synthesis early.
• Mutation-Specific Therapy – Currently, each mutation requires a separate therapy, making treatment slow and costly.

Genome editing does not involve the introduction of foreign genetic material while genetic engineering does.

• New Technique – PERT (Prime-Editing-mediated Readthrough of premature Termination codons).
• This technique uses a normal tRNA (transfer RNA) to create a suppressor tRNA permanently.
  • The suppressor tRNA bypasses early stop signals so a full protein is made.
• Hence, the PERT technique becomes applicable to many rare genetic diseases.

Protein synthesis happens when information passes from DNA to mRNA to tRNA and then to the ribosome.

• Mechanism – Human cells contain 418 tRNA genes. Leucine, arginine, tyrosine, and serine tRNAs are identified as promising candidates among them.
• Prime Editing – tRNA genes are hard to edit, so scientists used a special gene-editing method called prime editing with many guide RNAs to find the right spot.
• They also developed a new editing enzyme called PE6c, which made the process more accurate and effective.
• Key Results – Editing efficiency – 60–80% that is higher than the standard repair method at 10–20%.
• Restored enzyme activity in Batten disease, Tay-Sachs disease, etc. (17–70% of normal).
• No major off-target effects or toxicity observed.
• Challenges – Issues in delivery to different tissues, long-term safety, and durability.
• Clinical translation still requires further validation.
• Significance – Offers a single universal therapeutic platform for precision gene therapy with broad clinical applications in rare genetic disorders.

Quick Fact

Reference

TH | Single Genome-Editing Strategy for Multiple Genetic Disorders