Revolutionary Gene-Editing Platform Offers First Universal Treatment Path for Nonsense Mutation Rare Diseases
CAMBRIDGE, Mass., November 25, 2025 – Researchers at the Broad Institute of MIT and Harvard have published breakthrough findings on a universal gene-editing strategy that could transform therapeutic development for approximately 3,300 rare diseases caused by nonsense mutations. The study, released in the November 19 issue of Nature, validates the PERT (prime editing-mediated readthrough) system as the first platform capable of treating multiple unrelated genetic conditions with a single editing agent.
Nonsense mutations—premature stop signals that halt protein production—account for 24 percent of disease-causing variants documented in the ClinVar database and contribute to roughly one-third of all rare genetic disorders, including cystic fibrosis, muscular dystrophy, and Batten disease. Current gene-editing approaches require developing separate therapies for each individual mutation, a process costing millions of dollars and requiring years of development per treatment. The PERT system circumvents this limitation by making a universal edit that enables cells to bypass stop signals rather than correcting each mutation individually.
“We’re excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said David Liu, core institute member and director of the Merkin Institute for Transformative Technologies in Healthcare at the Broad Institute. Liu, who pioneered prime editing in 2019, noted that this approach could fundamentally alter the economics of rare disease drug development.
The research team, led by co-first authors Sarah Pierce and Steven Erwood, demonstrated PERT’s efficacy across multiple preclinical models. In human cell studies, the technology restored functional protein production in Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Mouse models of Hurler syndrome showed significant disease symptom alleviation following treatment. Critically, the study detected no off-target editing, toxicity, or disruption of normal RNA and protein production, addressing key safety concerns that have historically constrained gene-editing applications.
Market analysis indicates the rare disease therapeutics sector will exceed $300 billion globally by 2028, yet fewer than 5% of the estimated 10,000 known rare diseases have FDA-approved treatments. Early-stage funding remains a critical bottleneck; the National Organization for Rare Disorders (NORD) has awarded more than $9 million in research grants since 1989, directly contributing to two FDA-approved therapies. The PERT platform’s scalability could dramatically improve this efficiency ratio.
“The economics of rare disease drug development have long been unsustainable—spending $2 billion and 10-15 years per therapy for patient populations of fewer than 200 individuals, Medical Researcher Publishes Breakthrough in Rare Disease Understanding” said Dr. Sarah Pierce, postdoctoral associate and study co-lead. “PERT offers a viable path to treat multiple diseases simultaneously, potentially reducing development costs by 70% while accelerating clinical timelines.”
The Broad Institute has initiated partnerships with several biopharmaceutical companies to advance PERT toward Investigational New Drug (IND) applications. The institute projects first-in-human trials could begin within 24 months, targeting a basket trial design that would test the platform across multiple nonsense mutation diseases concurrently—a regulatory approach recently validated by the FDA’s approval of similar platform trials in oncology.
About the Broad Institute of MIT and Harvard
The Broad Institute is a world-leading biomedical and genomic research center dedicated to transforming medicine through collaboration. Established in 2004, the Institute brings together faculty from MIT, Harvard, and Harvard-affiliated hospitals to accelerate the understanding and treatment of disease. The Merkin Institute for Transformative Technologies in Healthcare focuses on developing and deploying breakthrough technologies to address critical unmet medical needs.
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