At the WIRED Health summit last week, Harvard biochemist and gene-editing pioneer David Liu says later this year his lab plans to report on a single gene-editing strategy that could treat many unrelated diseases. He calls it disease-agnostic therapeutic gene editing.
“It sounds sort of crazy, but there’s actually a very good molecular biology reason why this could be possible,” he told the audience in Boston, stopping short of details.
Gene-editing treatments are currently being developed for several rare and inherited genetic diseases. One gene-editing treatment, called Casgevy, is approved and available commercially to treat sickle cell disease and a related blood disorder called beta thalassemia. Earlier this year, KJ Muldoon, a baby boy born with an often fatal genetic disease that causes ammonia to build up in his blood, was saved with a customized gene-editing treatment—a medical first.
These treatments work by targeting specific mutations related to those diseases. But they can be costly to develop and must be designed for specific patient populations. Sometimes those patient populations can be very small, as in the case of baby KJ. His condition, called CPS1 deficiency, affects just one in 1.3 million live births.
Liu envisions a future in which one gene-editing approach could be used on multiple different diseases, regardless of what organ or tissue they affect or their genetic cause. He says this kind of streamlined strategy is needed because collectively, there are so many rare diseases, and it would be impractical to design treatments for each one. Global Genes, a rare disease advocacy organization, estimates that there are at least 10,000 rare diseases that affect more than 400 million people worldwide.
PHOTOGRAPH: VAIL FUCCI
“Genetic disease as a whole is not so rare. It’s actually many times more prevalent than cancer or HIV/AIDS,” Liu said. “We urgently need these ways to directly treat the root cause of these genetic diseases.”
Liu’s lab has developed two such ways to tackle rare diseases, base editing and prime editing. These next-generation versions of Crispr are already being used in around two dozen clinical trials around the world.
Base editing involves lab-made proteins that can change one DNA base, or “letter,” in a DNA sequence to another, such as changing a C to a T. They are akin to pencils that can correct single-letter misspellings. Baby KJ’s treatment used a base editor to treat his disease.
Prime editing, meanwhile, functions like a search-and-replace system for DNA. While traditional Crispr gene editing creates a double-stranded break in the DNA, prime editing allows for precise additions, deletions, or swaps without making that break. A prime editor, he explained, synthesizes a new segment of DNA and orchestrates repair processes in the cell, so that that new piece of DNA replaces the original sequence. Essentially, it’s a DNA word processor.
At WIRED Health, Liu teased that his lab has found a way to use prime editing in a disease-agnostic manner.
“Taking advantage of the ability of prime editing to do search-and-replace gene editing raises the possibility that a single composition of matter—potentially, a single drug—might benefit many, many more patients than going after diseases one mutation at a time,” Liu said. “That kind of future for gene editing, I think, will amplify, many fold its impact and, most importantly, its access to the patients who need these treatments.”
