Implications of the FDA’s new plausible mechanism framework for the development of a personalized in vivo prime editing platform

作者：Emily Feierman, Madelynn N. Whittaker, Aidan Quigley, Dominique L. Brooks, P. McVeigh, Angela X. Nan, Alvin Hsu, Hooda Said, Ousamah Younoss Soliman, Ryan C Giovenco, Beverly L. Davidson, Mohamad‐Gabriel Alameh, David R. Liu, Xiao Wang, Kiran Musunuru, Rebecca C. Ahrens-Nicklas · 发表于：The American Journal of Human Genetics · 年份：2026 · DOI：10.1016/j.ajhg.2026.03.018 · 被引用次数：1 · 研究领域：Biosimilars and Bioanalytical Methods、CRISPR and Genetic Engineering、Monoclonal and Polyclonal Antibodies Research

In February 2026, the US Food and Drug Administration (FDA) published a draft guidance on a new plausible mechanism framework for the development and approval of individualized therapies for genetic conditions. Here, we report initial proof-of-concept studies supporting a customizable prime editing platform geared to the treatment of 7 urea cycle disorders (UCDs) and other liver-centered disorders, as well as the outcome of a formal meeting with the FDA to discuss the use of the platform in an "umbrella-of-umbrellas" clinical trial including subjects with any of the 7 UCDs. We anticipate our findings will be of interest to academic investigators and industry sponsors who wish to pursue expeditious FDA approvals of therapies for ultra-rare diseases using the plausible mechanism framework.