Jennifer Gori, PhD, on the Potential of a Prime Editing Approach in Treating Chronic Granulomatous Disease

“I think prime editing has been a wonderful advance for the field. Other gene editing technologies, including Cas9 nuclease, may create a double-strand break, which can lead to potential off-target risks or imprecise edits. Prime editing does not create a double-strand break, and it's very precise. As a tool, it can be used to very elegantly repair any mutation in the genome."

Chronic granulomatous disease (CGD) is a rare inherited disease with symptoms that include a compromised immune system, chronic inflammatory conditions, and reduced life expectancy. The current standard of care is allogeneic hematopoietic stem cell transplant (HSCT), but this approach has drawbacks including the need for a matched donor and a risk of complications. As such, significant unmet need remains for this patient population.

Jennifer Gori, PhD, vice president of research at Prime Medicine, presented a study entitled “Prime editing of human CD34+ longterm hematopoietic stem cells precisely corrects the causative mutation of p47phox chronic granulomatous disease and restores NADPH oxidase activity in myeloid progeny” at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California. The study described preclinical research evaluating a novel approach to treating the autosomal recessive p47phox form of GCD with a prime edited autologous HSCT.

In an interview with CGTLive™, Gori described the novel approach and gave an overview of the study’s key results, emphasizing that over 92% editing was observed in long-term hematopoietic stem cells. She also discussed the potential advantages of prime editing compared to other gene editing approaches.

REFERENCE
Gori JL, Heath JM, Tedeschi JG, et al. Prime editing of human CD34+ long-term hematopoietic stem cells precisely corrects the causative mutation of p47phox chronic granulomatous disease and restores NADPH oxidase activity in myeloid progeny. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #101.