The FDA released draft guidance on using next-generation sequencing to assess gene-editing safety in human gene therapy products, focusing on off-target adverse effects and genome integrity risks. The document outlines how sponsors can design nonclinical studies that use sequencing and bioinformatics to evaluate both on- and off-target edit profiles. The agency emphasizes standardized approaches that could support safer progression from investigational new drug applications to later biologics license applications. FDA also notes that unintended edits can disrupt normal cell function and that adequate sequencing-based assessment is crucial. This draft guidance complements FDA’s broader gene-therapy frameworks for accelerated development of individualized therapies for ultra-rare diseases and prior guidance on human gene therapies incorporating genome editing. For biotech teams planning CRISPR and base-editing programs, the new draft provides a clearer blueprint for what regulators may expect in sequencing strategy—especially for nonclinical packages supporting first-in-human entry.