Pool-packaged AAV libraries exhibit extensive length-dependent and homology-dependent chimerism

Nature Biotechnology 2026 Open access

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Authors: Jean-Benoît Lalanne, Chau Huynh, John K. Mich, Avery C. Hunker, Troy A. McDiarmid, Haedong Kim, Boaz P. Levi, Jonathan T. Ting, Jay Shendure
DOI: 10.1038/s41587-026-03097-1
Cited by: 1
References: 68

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.

Fields of Study & Subjects

Virus-based gene therapy research Viral Infectious Diseases and Gene Expression in Insects RNA Interference and Gene Delivery

Publication details

Journal / source
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Publication date
28 April 2026
Language
EN