The FDA released draft guidance that lays out how sponsors should use next-generation sequencing (NGS) and bioinformatics to evaluate safety risks in genome-edited human gene therapy products. The draft focuses on off-target editing and chromosomal integrity, describing a nonclinical evidence strategy intended to be incorporated into IND submissions and biologics license applications. In its framework, the FDA outlines how sequencing can be designed to address on-target and off-target sites, including considerations such as when short-read sequencing may be sufficient for smaller edit footprints. The agency said the finalized guidance would standardize methods while supporting faster advancement of genome-edited therapies to patients. The draft also situates the guidance within the FDA’s broader plausible mechanism efforts for individualized therapies, emphasizing that unintended genome changes could disrupt normal cell function or create safety risks.