Research that empowers individuals to shape their own futures

David Liu has enjoyed considerable success.

On May 15, the New England Journal of Medicine released what has become a noteworthy case of a 5-month-old named KJ suffering from a lethal genetic condition who was the first to obtain a tailored CRISPR gene-editing treatment. This therapy was founded on base editing, a technique conceived in Liu’s lab nearly a decade prior.

The treatment aimed to rectify the single-letter genetic alteration impeding KJ’s capability to remove ammonia from his liver, a disorder referred to as CPS1 deficiency. Approximately half of infants with this condition do not survive their first week. KJ not only lived but started to show signs of recovery.

This marked the first of two significant recent occurrences involving research pioneered by Liu, the Thomas Dudley Cabot Professor of the Natural Sciences, and his team. Liu, who is also an HHMI investigator, received the 2025 Breakthrough Prize for his contributions to base editing and prime editing, solutions that permit the modification or substitution of nearly any genetic mutation.

“There’s a lot of assurance in base editing technology based on the 17 preceding clinical trials and thousands of scholarly articles, but that doesn’t diminish the reality that the stakes are extremely high for this patient and their family,” Liu remarked regarding KJ’s situation. “This narrative powerfully illustrates that the editing methods, delivery technology, manufacturing, animal studies, and regulatory endorsement are sufficiently robust to facilitate this large collaborative effort promptly to save Baby KJ.”

A chemical biologist by background, Liu has consistently asserted that scientific advancement grants people more control over their life trajectories.

Just a week following KJ’s report gaining widespread attention, Prime Medicine, a biotech firm co-founded by Liu, released the initial clinical outcomes of its therapy for chronic granulomatous disease (CGD), a rare and serious immune condition.

For the first time, an adult subject had undergone treatment with a prime-edited therapy. Prime editing facilitates even more adaptable and precise modification of DNA.

The patient lacked two base pairs in a specific gene that codes for an enzyme crucial for immune system functioning. The adult patient showed positive results: Preliminary data indicated restoration of the absent enzyme activity with no significant side effects.

“This is the Alyssa Tapley moment for prime editing,” Liu stated, alluding to the first patient successfully treated with base editing in the U.K. “The researchers at Prime Medicine managed to extract the patient’s bone marrow, edit it via prime editing, and then reintroduce the modified bone marrow back into their body.

“Until now, the only potentially curative method for CGD has been the transplantation of bone marrow from another individual, which poses significant risks of rejection or graft-versus-host disease, where the donor’s immune system attacks the patient’s own tissues,” he added. “Thus, prime editing offers a particularly elegant and effective remedy, by prime editing the patient’s own bone marrow to remedy the disease-causing deletion and then reintroducing it to the patient.”

In KJ’s case, the treatment was formulated on an expedited schedule by a coalition of academic researchers and companies across the U.S., spearheaded by University of Pennsylvania physician scientists Kiran Musunuru and Rebecca Ahrens-Nicklas.

Liu’s laboratory played a crucial role in the creation of base editing nearly eight years ago and provided guidance to the team on
“““html

Which base editor would be most likely to effectively rectify KJ’s mutation while reducing the chance of unintended consequences?

“Typically, it requires numerous years to transition from a genetic identification of a new mutation to a therapeutic intervention,” Liu stated. “This instance, it occurred in under seven months.”

Although base editing and prime editing technologies each have unique advantages, their common potential is a future where previously unmanageable genetic disorders could be remedied with a personalized approach.

Prime editing, unveiled by Liu’s team in 2019, functions like a molecular word processor, capable of search-and-replace modifications to DNA. It paves the way for addressing thousands of genetic mutations linked to ailments such as sickle cell disorder, progeria, and Tay-Sachs disease.

Both KJ’s situation and the CGD advancement exemplify what Liu has persistently advocated for: the conversion of foundational science into innovations that can transform lives — reliably, swiftly, and justly.

“Genetic disorders arise due to the chemical configuration of our DNA, which means they will always be part of humanity. Our objective is to create a future where such forms of gene editing therapies are commonplace, allowing individuals to no longer be so influenced by the errors in our DNA,” Liu commented. “We can finally exercise some control over our genetic traits.”

Liu acknowledged initial funding from the National Institutes of Health and other governmental bodies for facilitating high-risk, high-reward concepts like gene editing. He cautioned that fundamental science and future advancements are under significant threat due to funding reductions in scientific research by Washington.

“It’s simple to overlook that each instance of scientific advancement translating into a societal benefit began as a fundamental scientific inquiry where there may not have been an apparent route to serving society,” Liu remarked. “A fundamental study of repetitive DNA sequences found in bacteria led to the discovery of CRISPR and now to numerous applications of gene editing to aid patients suffering from severe diseases, highlighting the vital role of basic science in humanity. Basic research must be backed if we aspire for our children to have the chance for improved lives.”

More like this

• 
  

  Rewriting genetic destiny

  David Liu, recipient of the Breakthrough Prize, navigates the journey to an ‘incredibly exciting’ disease combatant: ‘This is the essence of fundamental science.’

“`