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News: Researchers from the Broad Institute recently reported a new gene-editing strategy called Prime Editing–Mediated Readthrough of Premature Termination Codons (PERT) that may enable a single treatment to address many genetic diseases caused by nonsense mutations.
About Prime Editing–Mediated Readthrough of Premature Termination Codons (PERT)
- PERT is a genome-editing strategy designed to treat genetic diseases caused by nonsense mutations, which prematurely halt protein production.
- Problem addressed – Nonsense mutations introduce premature termination codons (PTCs) in mRNA, causing early stoppage of translation and resulting in incomplete, nonfunctional proteins responsible for many inherited disorders.
- Core technology used – PERT is based on prime editing, an advanced CRISPR/Cas9-based system that works as a precise “search-and-replace” tool and does not create double-strand breaks in DNA.
- Key mechanism – PERT does not directly correct the disease-causing mutation. Instead, it inserts an engineered suppressor transfer RNA (tRNA) into the genome.
- Role of suppressor tRNA – The engineered tRNA recognizes premature stop codons and inserts an amino acid in place of the stop signal, enabling the ribosome to continue translation and produce a full-length functional protein.
- Unique feature – The suppressor tRNA is inserted at a redundant tRNA gene site, ensuring stable expression without disrupting essential genes, and making the strategy independent of the specific mutated gene.
- Advantages & Limitation – A single PERT-based therapy could potentially treat multiple unrelated genetic diseases caused by nonsense mutations, reducing time and cost of drug development; however, the technology is still in early research stages and requires further animal and clinical testing to establish safety and long-term efficacy.
