Broad Institute Scientists Pioneer New Prime Editing Approach to Target Hundreds of Genetic Diseases

CAMBRIDGE, MA – November 20, 2025 — Researchers led by David Liu at the Broad Institute have published new work in Nature describing a novel application of prime editing that could address dozens, or potentially hundreds, of genetic diseases sharing a common root cause: nonsense mutations. This ambitious approach leverages gene editing to correct errors in the body’s protein-making machinery.

The strategy, which has the potential to treat diseases like cystic fibrosis, Tay-Sachs disease, and various rare disorders, offers a possible “one-size-fits-many” solution, moving away from the costly, disease-specific therapies currently required for rare genetic ailments.

Patching Broken Protein Instructions with Suppressor tRNA

The new technique focuses on diseases caused by nonsense mutations, genetic errors that prematurely introduce a “stop” sign (stop codon) into the DNA instructions. These errors account for 24% of all disease-causing variants. The misplaced stop signal prevents the creation of a full-length, functional protein, leading to diseases like Duchenne muscular dystrophy.

Liu’s group uses prime editing—a highly precise form of gene editing developed in his lab—to install suppressor tRNAs (transfer RNAs).

• tRNAs are key molecules that typically read genetic instructions to assemble proteins.
• The newly installed suppressor tRNAs effectively “patch over” the misplaced stop codon, allowing the body to produce the full, functional protein.

“The field needs, and will benefit from, creative ways to use gene editing so that one composition of matter—notionally, one drug—can benefit many different patients, regardless of their specific mutation, or regardless of even which disease they have,” Liu stated.

Challenges Remain in Delivery and Translation

While the work is hailed as a “step change” in therapeutic design, significant obstacles remain, particularly concerning delivery into the human body. The approach has only been tested in cells in a dish and in mouse models of Batten disease, Tay-Sachs disease, cystic fibrosis, and Hurler syndrome.

In the Hurler syndrome mouse model, the researchers used AAV delivery system for implementation.

• High doses of certain AAV vectors required to reach certain tissues in humans have been associated with toxicities and patient deaths, making translation difficult, especially for non-liver/blood diseases.

Fyodor Urnov, a molecular therapeutics professor at UC Berkeley not involved in the study, emphasized the delivery hurdle: “Putting that into a person to have a therapeutic outcome is a problem in a different dimension.”

Liu acknowledged that liver and blood diseases offer “the shortest path” to the clinic, but stated that better delivery methods are being developed for organs like the brain, heart, and muscles. The research suggests that about a dozen prime editor reagents could cover most diseases caused by premature stop signals.

Liu’s biotech company, Prime Medicine, is reportedly interested in the tRNA approach, and Liu’s soon-to-come nonprofit, the Center for Genetic Surgery, plans to advance the research for rare diseases that lack commercial incentive.