Adeno-associated virus (AAV) vector gene therapies deliver a functional or partially functional transgene to treat genetic disease through a single, typically intravenous, administration, and represent a mechanistically distinct category from both small-molecule and conventional biologic therapeutics. At least one AAV-based micro-dystrophin gene therapy has received regulatory approval for Duchenne muscular dystrophy, establishing a labelled risk profile, including acute liver injury, myocarditis, immune-mediated myositis, and thrombotic microangiopathy, that directly shapes nonclinical safety assessment for this product category. This article develops a complete, IND-enabling nonclinical toxicology and immunogenicity strategy for AAV-based gene therapies in this indication, built on FDA guidance for cellular and gene therapy products, gene therapy products incorporating a disease-relevant animal model, shedding and biodistribution assessment, and long-term follow-up. The package integrates test-article supply planning expressed in vector genomes per kilogram, a dual-rodent-model design using both a disease-relevant strain and a wild-type comparator, a non-human-primate pivotal safety study with cardiovascular telemetry and recovery, a comprehensive immunogenicity and toxicokinetic assessment program, biodistribution and shedding studies addressing environmental release and germline risk, and a waiver-rationale approach to classical reproductive and genotoxicity testing appropriate for a non-integrating viral vector. Beyond the specific case, the article develops general principles for translating labelled clinical risks directly into nonclinical safety endpoints, and closes with recommendations for the nonclinical section of an IND application for this drug category. Keywords: AAV gene therapy; Duchenne muscular dystrophy; micro-dystrophin; immunogenicity; biodistribution; shedding; IND application; FDA gene therapy guidance