Pool-packaged AAV libraries exhibit extensive length-dependent and homology-dependent chimerism.
basic_science · Level V
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- Record sourced from PubMed, PMID 42050331.
- Also identified by DOI 10.1038/s41587-026-03097-1.
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Abstract
Adeno-associated viruses (AAVs) are preferred gene therapy vectors because of their versatility, durability and safety profile. Here, we demonstrate extensive chimerism, manifesting as pervasive barcode swapping, among complex recombinant AAV (rAAV) 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 rAAV genomes. These results have implications for the design and deployment of functional rAAV libraries.