The proposed guidance builds on the groundbreaking work of a team at Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania, which last year developed a first-of-its-kind gene-editing therapy for a baby named KJ. The treatment was tailored specifically to his unique genetic mutation, a process that typically takes years but was compressed into months.

Kiran Musunuru, a professor of cardiovascular medicine at Penn and a member of the CHOP team, and Rebecca Ahrens-Nicklas, a pediatric neurologist at CHOP, led the effort behind the therapy. Their work demonstrated that it is possible to design, test, and deliver a customized gene-editing treatment for a single patient with a rare disease.

The new draft guidance, which the FDA released in recent weeks, aims to provide a clearer regulatory pathway for such personalized therapies, often called "n-of-1" treatments because they are designed for one patient. The guidance could make it easier for academic medical centers and small biotechnology companies to bring similar treatments to patients with ultra-rare diseases, many of which currently have no approved therapies.

"This is a significant step forward for the field," said Musunuru, who also directs the Cardiovascular Institute at Penn. "It gives researchers and clinicians a framework to navigate the regulatory process and ultimately help more patients."

The draft guidance comes as gene-editing technologies, particularly CRISPR-based approaches, are advancing rapidly. In 2023, the FDA approved the first CRISPR-based therapy for sickle cell disease, a milestone that underscored the potential of gene editing to treat genetic disorders. However, personalized therapies for individual patients pose unique regulatory challenges, including how to demonstrate safety and efficacy when only one person receives the treatment.

The CHOP team's work on Baby KJ, whose story was widely reported, involved identifying the genetic cause of his severe condition, designing a custom CRISPR-based therapy, and receiving FDA permission to treat him under an expanded access protocol. The treatment was administered in 2025, and KJ has since shown signs of improvement.

The proposed guidance is now open for public comment, and stakeholders across the biomedical community are expected to weigh in. Patient advocacy groups have welcomed the move, saying it could bring hope to families affected by rare diseases that have long been overlooked by traditional drug development.

"For families with children who have ultra-rare conditions, this guidance represents a lifeline," said Dr. Ahrens-Nicklas. "It acknowledges that one-size-fits-all approaches don't work for everyone and that we need to be able to move quickly when time is of the essence."

The FDA is expected to finalize the guidance after reviewing public comments, a process that could take several months. If finalized, the guidance would not be legally binding but would provide a roadmap for developers seeking to bring personalized gene therapies to market.

Philadelphia's role in shaping the policy reflects the region's growing prominence in gene therapy research, with institutions like CHOP, Penn, and Jefferson University contributing to a cluster of innovation that has attracted significant investment and talent. The city has become a hub for cell and gene therapy, with dozens of companies and research centers focused on developing new treatments for cancer, genetic disorders, and other diseases.

For now, the draft guidance offers a glimpse of how regulators might adapt to the rapidly evolving field of personalized medicine, and Philadelphia scientists are proud to have played a part.

"This is a testament to the collaborative spirit here in Philadelphia," Musunuru said. "We're not just doing science for the sake of science; we're trying to translate it into treatments that can help real people."