PERT: Genome Editing Strategy

18 Feb 2026

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.

Key Concepts

PERT: Prime-Editing-mediated Readthrough of Premature Termination codons.
CRISPR-Cas9: Clustered Regularly Interspaced Short Palindromic Repeats – CRISPR associated protein 9.
Repurposing genes: This refers to modifying an existing gene to perform a new therapeutic function different from its original biological role.
pegRNA: Prime Editing Guide RNA.
- Guides the editing enzyme to a specific DNA site.
- Provides the template for precise genetic correction.
NMD: Nonsense-Mediated Decay.
- A cellular mechanism that degrades faulty mRNA containing premature stop codons.

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.

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About Genetic Disorders

Genetic disorders are diseases or conditions caused by abnormalities in an individual’s genes or chromosomes, which may be inherited or arise due to spontaneous mutations.
- For Example: Down syndrome, Turner syndrome
Causes
- Gene mutations (e.g., point mutations, insertions, deletions)
- Chromosomal abnormalities (structural or numerical changes)
- Errors during cell division (meiosis/mitosis)
- Environmental factors inducing mutations

About Codons

Codons are sequences of three nucleotides in messenger RNA (mRNA) that specify a particular amino acid or signal the termination of protein synthesis during translation.
Each codon consists of 3 nitrogenous bases (triplet code).
Types of Codons:
- Start Codon:
  - AUG → Codes for Methionine and initiates protein synthesis.
- Stop Codons: UAA, UAG, UGA
Role in Protein Synthesis
- During translation, ribosomes read mRNA codons.
- Each codon pairs with a complementary anticodon on tRNA.
- Ensures correct sequence of amino acids in protein formation.

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