A new gene-editing technique known as PERT has shown the ability to correct a wide range of disorders caused by “nonsense” mutations, including forms that interfere with haemoglobin production. The method, described in a study published in Natureoffers a potential single-tool solution for conditions previously requiring custom-designed treatments.
How the new tool PERT targets genetic disease
PERT, short for Prime Editing with RNA-mediated Translational ReadThrough, combines prime editing technology with engineered suppressor tRNAs. These synthetic tRNAs instruct the cell’s protein-making machinery to read through premature stop signals created by nonsense mutations. Such mutations account for nearly one-quarter of all known disease-causing DNA variants, making them a major challenge in treating inherited disorders.By enabling the cell to produce full-length, functional proteins even when the DNA contains a truncating mutation, PERT provides a powerful new strategy for repairing genetic disease at its root.
The study behind the breakthrough
The Nature study, led by David Liu and colleagues at the Broad Institute of MIT and Harvard, demonstrated the PERT system in both human cell cultures and mouse models. Their results showed that PERT could bypass harmful stop codons and restore protein production across multiple genes linked to disease.By inserting the suppressor tRNA gene directly into the genome using prime editing, the approach may offer long-lasting effects without repeated dosing. This represents a major improvement over earlier methods that relied on viruses or lipid nanoparticles, which often required multiple treatments and carried safety concerns.
Implications for haemoglobin disorders
Among the conditions PERT could potentially treat are haemoglobin-related diseases, including certain forms of beta-thalassaemia in which nonsense mutations disrupt normal haemoglobin production. By overriding these premature stop signals, PERT may restore healthy protein synthesis and reduce the need for lifelong therapies or invasive procedures.
Why the advance matters
Current gene-editing therapies typically target a single mutation or disease, making development slow and expensive. PERT’s disease-agnostic design could drastically speed up the creation of treatments and broaden the number of patients who benefit. If proven safe and effective in humans, it could become one of the most versatile gene-editing tools ever developed.David Liu noted that such an approach “raises a possibility that would be incredibly exciting for patients,” particularly those with conditions caused by truncating mutations.
What comes next
Although highly promising, PERT remains in early preclinical testing. More work is needed to assess its safety, reliability and effectiveness across different tissues before human trials begin. Researchers will also need to determine how durable and precise the system is once integrated into the genome.Still, the Nature study represents a major step toward a single therapeutic platform capable of treating a broad spectrum of inherited diseases, including those once thought untreatable.
