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After decades as a therapeutic modality largely confined to the academic research environment, gene therapy has emerged in recent years as a rapidly expanding therapeutic approach in the biopharmaceutical industry with AAV as the most commonly used viral vector for gene delivery. This interest in the field of gene therapy by industry has been enhanced by the recent success of approved therapies for curing genetic diseases such as ZOLGENSMA for spinal muscular atrophy and LUXTURNA for Leber congenital amaurosis. However, recently reported clinical and nonclinical toxicities highlight the challenges in safely developing AAV gene therapies that require high dose systemic administration. The presentation reviewed general attributes of AAV as a gene therapy vector, clinical and nonclinical liver toxicity associated with AAV gene therapy and the potential for a multimodal immune suppression strategy that may mitigate toxicities.<\/jats:p>","DOI":"10.1177\/01926233231201408","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T08:43:30Z","timestamp":1695977010000},"page":"400-404","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":59,"title":["An Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy"],"prefix":"10.1177","volume":"51","author":[{"given":"Laurence O.","family":"Whiteley","sequence":"first","affiliation":[{"name":"Pfizer Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"bibr1-01926233231201408","doi-asserted-by":"publisher","DOI":"10.1177\/0192623318803867"},{"key":"bibr2-01926233231201408","unstructured":"Audentes Therapeutics Inc (An Astellas Company) Docket No. FDA-2021-N-0651. 2021 meeting materials, cellular, tissue and gene therapies advisory committee, September 2-3, 2021. 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