Adeno-associated viral vectors are currently the most commonly used vectors for gene editing and gene replacement approaches in both CNS and ocular indications. The first part of the presentation will cover case by case considerations for making decisions about nonclinical program design to enable clinical trials of AAV-mediated gene therapies. These will include communication with clinical team members; interactions with regulatory authorities; planning for formulation and delivery of test articles; planning for analytical methods to support toxicology studies; decisions about model selection and justification; dose selection; and study design.

In the second part of the presentation, general regulatory expectations for nonclinical testing of a CRISPR-based gene editing therapeutic will be discussed, including expectations for evaluation of genotoxicity including off-target editing, characterization of gross chromosomal changes, and evaluation of tumorigenicity.