biostudies-literatureUnknownLalanne JBNIMH NIH HHSNHGRI NIH HHSAdeno-associated viruses (AAVs) have emerged as the foremost gene therapy delivery vehicles due to their versatility, durability, and safety profile. Here we demonstrate extensive chimerism, manifesting as pervasive barcode swapping, among complex AAV libraries that are packaged as a pool. The observed chimerism is length- and homology-dependent but capsid-independent, in some cases affecting the majority of packaged AAV genomes. These results have implications for the design and deployment of functional AAV libraries in both research and clinical settings.bioRxiv : the preprint server for biology2025.01.14.632594https://www.ebi.ac.uk/biostudies/studies/S-EPMC11761685biostudies-literatureExtensive length and homology dependent chimerism in pool-packaged AAV libraries.PMC11761685R01 HG010632UF1 MH128339McDiarmid TALevi BPLalanne JBShendure JTing JTHunker ACHuynh CMich JKfalseExtensive length and homology dependent chimerism in pool-packaged AAV libraries.Adeno-associated viruses (AAVs) have emerged as the foremost gene therapy delivery vehicles due to their versatility, durability, and safety profile. Here we demonstrate extensive chimerism, manifesting as pervasive barcode swapping, among complex AAV libraries that are packaged as a pool. The observed chimerism is length- and homology-dependent but capsid-independent, in some cases affecting the majority of packaged AAV genomes. These results have implications for the design and deployment of functional AAV libraries in both research and clinical settings.2025-01-01T00:00:00Z2025 Jan2025-04-05T11:34:21.63Z2025-04-05T11:34:21.63ZS-EPMC117616853986834110.1101/2025.01.14.632594