Being Our Own Worst Critic

June 17, 2026 by Kyle Studey

Working to reach scalable treatment approaches

When both ASGCT and TIDES came to Boston at the same time this year, there was an unmistakable energy of scientific collaboration, equal parts inspiring and chaotic. Perfectly capturing this idea was none other than Dr. Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine. He was scheduled at both events on the same day, yet what he had to say was impactful no matter where he spoke.

It was not a review of the incredible work leading to the first personalized CRISPR gene-editing therapy in 2025. No, he proclaimed that wasn’t even science; “It was not a clinical trial. It was not clinical research. It was not a cure.”

While the entire world seems to be celebrating the achievements of Musunuru and Dr. Rebecca Ahrens-Niklas of Children's Hospital of Philadelphia (CHOP), Musunuru took a significantly more reserved approach. Rather than amplifying these celebrations, Kiran reframed them, urging caution and the importance of not overselling these early breakthroughs. He stood next to a simple white slide containing just seven words:

“You should be your own worst critic.”

Musunuru’s focus was not on celebrating a single success, but on confronting the much larger challenge ahead; how to translate an individualized (N-of-1) therapy into a scalable treatment approach for patients with Urea Cycle Disorders (UCDs). He described the multitude of FDA interactions needed to establish a clinical plan addressing the several possible mutations across seven different genes known to cause a UCD. This “umbrella of umbrellas,” as he calls it, would consist of seven different IND filings (one for each gene and all its variants) that fall under an overall Master Protocol in a Phase I/II-like Proof-of-Concept Stage.

As enough information is gathered for a particular gene, they can be moved into the Phase III-Like Evaluation Phase. Data will continue to be generated on a rolling basis for each of the other genes, creating a constant feedback loop of data across the different INDs. The hope is that individual BLA’s can be filed using the FDA’s recently announced plausible mechanism framework.

The plan was ambitious, innovative, and daunting, especially given the small team Musunuru and Ahrens-Niklas have. As it stands, a single IND has been filed and accepted; it likely will not be until 2027 that all seven are finalized and the trial work can begin.

As he left the stage, that simple white slide stuck with me. The first personalized gene editing therapy has already changed the life of a young boy, the culmination of decades of scientific innovation. But transforming personalized medicine from headline breakthrough to standard of care will require much more than a single success. It will demand continued innovation in development tools and manufacturing processes, significant reductions in cost and timelines, close collaboration with regulators to enable novel clinical models, and an unwavering commitment to quality across the entire value chain.

Kiran Musunuru and Rebecca Ahrens-Niklas have taken a critical first step. But realizing the full potential of personalized gene therapy will require a coordinated effort across the entire industry. If this field is to succeed, we must share Musunuru’s mindset; push forward relentlessly, while always remaining our own worst critics.

• Have questions on this topic? Contact Us
• Learn more about Baby KJ’s treatment
• Visit the Gene Editing section of our website
• View our CRISPR page
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