The State Of Gene Editing - EP 37 Eryney Marrogi
Timestamps are as accurate as they can be but may be slightly off. We encourage you to listen to the full context.
Podcast Summary
In this fascinating Core Memory podcast episode, Ashley Vance interviews Dr. Ernie Morogi, a medical student and former researcher who bridges the worlds of cutting-edge biology and practical medicine. The conversation centers around the groundbreaking case of Baby KJ, the first infant to receive a personalized gene therapy designed specifically for his rare genetic condition. (16:36) Baby KJ was born with CPS1 deficiency, a life-threatening metabolic disorder that prevents the body from processing protein properly, leading to dangerous ammonia buildup in the blood.
- Main Themes: The episode explores how a multi-year collaborative effort between researchers at institutions like Harvard, MIT, and CHOP created a framework for rapidly developing personalized gene therapies for rare diseases, demonstrating that we now have the tools to fix single-gene disorders in real-time.
Speakers
Ashley Vance
Ashley Vance is the host of Core Memory and a renowned technology journalist. He previously worked as a senior writer for Bloomberg Businessweek and wrote for The Register, covering semiconductors and data center technology. Vance has authored several books including biographies of tech figures and is known for his in-depth reporting on innovative companies and emerging technologies.
Dr. Ernie Morogi
Dr. Ernie Morogi is a medical student with an extensive background in cutting-edge biological research. He previously worked in George Church's lab at Harvard/MIT, focusing on gene editing and synthetic biology, and later joined Dyno Therapeutics working on machine learning applications for viral delivery systems. Morogi has become a prominent science writer, particularly known for his detailed coverage of gene therapy breakthroughs including the Baby KJ case.
Key Takeaways
Personalized Gene Therapy is Now Feasible for Rare Diseases
The Baby KJ case demonstrates that we have reached a critical milestone where personalized gene therapies can be developed rapidly for rare genetic conditions. (43:12) Unlike previous gene therapies that targeted common mutations affecting many patients, KJ received a therapy designed specifically for his unique genetic profile within just five months of diagnosis. This represents a dramatic acceleration from the typical decade-long development timeline for gene therapies. The success shows that all the necessary components - precise editors, effective delivery systems, and regulatory pathways - are now mature enough to enable truly personalized medicine for monogenetic disorders.
Collaborative Infrastructure Enables Rapid Response
The breakthrough wasn't accidental but resulted from years of systematic preparation by a collaborative network of researchers. (23:37) Teams at institutions like Harvard, MIT, the Broad Institute, and IGI Berkeley spent two years developing a standardized "playbook" for responding to rare genetic diseases. They practiced with hypothetical cases, established relationships with industry partners, and created processes for everything from cell line creation to regulatory approval. This infrastructure allowed them to spring into action when Baby KJ was born, treating the real case like a well-rehearsed drill rather than a crisis.
Gene Editing Requires Strategic Target Selection
Successful gene therapy depends on a three-part framework that Morogi outlines: where to go (target organ), what to fix (specific gene), and duration of effect (temporary or permanent). (30:29) Baby KJ's case was ideal because his liver was the clear target organ, the CPS1 gene mutation was well-understood, and a permanent fix was needed. This framework helps explain why some diseases remain challenging - complex conditions like Alzheimer's or ALS lack clear single targets, making them unsuitable for current gene therapy approaches despite having sophisticated editing tools.
Manufacturing and Regulation Present Major Cost Barriers
While the science of gene editing has matured, practical deployment faces significant economic hurdles. (59:00) Current gene therapies can cost millions of dollars, largely due to expensive manufacturing processes that require sterile facilities and specialized reagents. Morogi suggests costs could potentially drop to "low hundreds of thousands" of dollars with improved manufacturing and more flexible regulatory frameworks. The FDA's willingness to work with the KJ team on an accelerated timeline suggests regulatory adaptation is possible, but systematic changes are needed to make these therapies accessible.
China is Rapidly Gaining Ground in Gene Therapy Implementation
While the US leads in fundamental research, China is increasingly competitive in clinical deployment of gene therapies. (66:06) Approximately one-third to half of all gene therapy trials now occur in China, where regulatory frameworks allow faster progression from laboratory to clinic. Chinese researchers can take academic discoveries made in America and deploy them clinically years faster than in the US system. This creates a concerning dynamic where American taxpayer-funded research benefits are realized abroad first, potentially shifting the global balance of biotech leadership.
Statistics & Facts
- Baby KJ received his personalized gene therapy just 5 months after diagnosis, compared to the typical 10-year development timeline for gene therapies like those for sickle cell disease. (43:12)
- The therapy achieved approximately 42% editing efficiency in KJ's liver cells, which proved sufficient to reduce his medication needs by 50%. (34:23)
- CPS1 deficiency affects only 1 in 1.5 million births, making it an extremely rare condition with a 50% mortality rate if untreated. (47:03)
