PERT: Genome Editing Strategy

A recent study published in Nature reported a new genome-editing strategy called PERT (Prime-Editing-mediated Readthrough of Premature Termination codons).

• The study offers a single, gene-agnostic therapy to treat multiple diseases caused by nonsense mutations.
• Developed by researchers from the Broad Institute, Harvard University, and University of Minnesota.

About PERT (Prime-Editing-Mediated Readthrough of Premature Termination Codons)

• PERT is a novel genome-editing strategy that uses prime editing to enable readthrough of premature termination (stop) codons, thereby restoring production of full-length functional proteins in genetic disorders caused by nonsense mutations.
• Repurposing genes and pegRNA is an essential component of it.
• Mechanism of PERT:
  • Uses a modified CRISPR–Cas system combined with reverse transcriptase.
  • Instead of fully correcting the mutation, PERT modifies the stop codon region.
  • It enables the cellular machinery to bypass (read through) the premature stop codon.
  • As a result, translation continues and production of near-normal functional protein.
• Challenge: Its Key challenges remain, particularly around delivery, long-term safety, and performance across different tissues.
• Applications:
  • It is helpful in curing diseases such as Cystic fibrosis, Beta thalassemia.
  • It is more precise and potentially safer than traditional CRISPR editing.
  • It may treat multiple disorders caused by nonsense mutations using a similar strategy
  • It reduces risk of off-target genome damage.

Explore Combo (GS+Optional) Courses

Explore Combo (GS+Optional) Courses

About Nonsense Mutations

• A nonsense mutation is a type of point mutation in which a single nucleotide substitution converts a codon encoding an amino acid into a stop codon (UAA, UAG, UGA), resulting in premature termination of protein synthesis.
• Nonsense mutations account for about a quarter of all known disease-causing genetic changes.
• Mechanism
  • Occurs due to base substitution in DNA.
  • The altered codon signals termination during translation.
  • Produces a truncated (shortened) and usually non-functional protein.
  • May trigger Nonsense-Mediated Decay (NMD), leading to degradation of faulty mRNA.

Check Out UPSC CSE Books

Visit PW Store

DOWNLOAD PDF