Analysis of vector genome integrations in multicentric lymphoma after AAV gene therapy in a severe hemophilia A dog.

ABSTRACT: Adeno-associated viral (AAV) vectors have traditionally been viewed as predominantly nonintegrating, with limited concerns for oncogenesis. However, accumulating preclinical data have shown that AAV vectors integrate more often than previously appreciated, with the potential for genotoxicity. To understand the consequences of AAV vector integration, vigilance for rare genotoxic events after vector administration is essential. Here, we investigate the development of multicentric lymphoma in a privately owned dog, PC9, with severe hemophilia A that was treated with an AAV8 vector encapsidating a B domain-deleted canine coagulation F8 gene. PC9 developed an aggressive B cell lineage multicentric lymphoma 3.5 years after AAV treatment. Postmortem analysis of the liver, spleen, and lymph

SUBMITTER: Van Gorder L 

PROVIDER: S-EPMC10716008 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature