The FDA released draft guidance on how to assess safety risks in genome-edited gene therapies using next-generation sequencing and bioinformatics. The agency’s focus includes off-target editing and loss of genome integrity, with proposed nonclinical study designs intended to support IND submissions and biologics license applications. FDA Commissioner Marty Makary said the agency is “serious about moving this ball forward,” while the draft document outlines how sponsors should incorporate sequencing strategies into nonclinical assessments. The guidance highlights that adequate evaluation of chromosomal integrity is needed to minimize unintended changes. The draft also references standardized methods for evaluating on- and off-target edits, noting that short-read strategies may be sufficient for certain types of edit footprints. The move aligns with the FDA’s broader “plausible mechanism” and framework efforts to speed development of individualized therapies.