The Implications of the First Successful Personalized Gene Editing Therapy
Kiran Musunuru, MD, PhD, and Rebecca Ahrens-Nicklas, MD, PhD, physician-scientists at CHOP, discussed long-term future expectations for personalized gene editing therapy.
This is the third part of an interview with Kiran Musunuru, MD, PhD and Rebecca Ahrens-Nicklas, MD, PhD. For the first part, click here. For the second part, click here.
Kiran Musunuru, MD, PhD
Credit: Perelman School of Medicine
Rebecca Ahrens-Nicklas, MD, PhD
Credit: CHOP
A major milestone in the history of gene editing was made recently when KJ, a child with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, was treated by Children’s Hospital of Philadelphia (CHOP) investigators in an n-of-1 clinical trial for a personalized CRISPR-based gene editing therapy for his condition. KJ's case was covered in a paper in The New England Journal of Medicine published on May 15, 2025, and a presentation at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2024, in New Orleans, LA.1,2
At ASGCT's meeting, CGTLive® sat down with trial investigators Kiran Musunuru, MD, PhD, a physician-scientist and Barry J. Gertz Professor for translational research in the Perelman School of Medicine at the University of Pennsylvania and CHOP and Rebecca Ahrens-Nicklas, MD, PhD, a physician-scientist and director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at CHOP, to discuss the bigger implications of KJ's treatment. They spoke about how the technology used to treat KJ may eventually be applied in a much broader context and also stressed the importance of collaboration in carrying out the trial.
CGTLive: How would you summarize the big picture implications that doctors and the broader healthcare community should take away from this story?
Kiran Musunuru, MD, PhD, MPH, ML, MRA: I think this is an early step—I won't say the first step—but an early step in a totally new type of medicine. Right now medicine is dominated by chronic therapies, many pills you have to take every day for the rest of one's life, which is really a big burden to put on patients and it's no surprise that adherence is far south of 100%. If we can move to a mode where, whether it's an ultra-rare disease or the leading cause of death worldwide, you can give a therapy that has a durable effect that will last for a very long time, potentially even a lifetime, you relieve patients of the burden of having to take therapies again and again and again, which brings up issues of adherence and accessibility and cost and so forth. It's really moving medicine to be more like surgery in a way—more like a type of procedural healthcare where you're doing one-time interventions that have durable, long-term therapeutic effects. I fully suspect that as this takes off in the coming years—and maybe it'll take more like decades—but we'll eventually get to the point where gene editing will be the standard of care for many diseases, ranging from ultra-rare to the most common diseases. We might get to the point where it's so routine that [it’s similar to] the way we think about antibiotics and blood pressure medications, now. You don't even think twice about it, right? You get sick, you take an antibiotic, right? That might be the role gene editing therapies have to play in keeping us healthy.
Is there anything else you want to add?
Rebecca Ahrens-Nicklas, MD, PhD: This was an effort, really, to help one really sick baby. But it has been amazing because in order to actually make that effort a reality, or at least attempt to help this baby, it required a team of so many people, and not just people at our institutions, but really—once we realized that this might be possible to try—we reached out to academic colleagues, industry colleagues, governmental colleagues from around the country and the world for help—and we are just so grateful that everybody essentially said yes. People everywhere dropped what they were doing to help us, to try to help KJ. Without the help of our industry partners, our academic partners, and really the leadership of colleagues at the National Institutes of Health who helped support this, this wouldn't have been possible. As such, I think one of the big lessons I've learned from all of this is that collaboration is absolutely essential in order to help our rare disease patients and really, I've just been so impressed by everyone who said yes and helped us.
This transcript has been edited for clarity.
Click here to view more coverage of the 2025 ASGCT Annual Meeting.
