Lalanne Jean-Benoît, Mich John K, Huynh Chau, Hunker Avery C, McDiarmid Troy A, Levi Boaz P, Ting Jonathan T, Shendure Jay
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC, Canada.
bioRxiv. 2025 Jan 15:2025.01.14.632594. doi: 10.1101/2025.01.14.632594.
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.
腺相关病毒（AAV）因其多功能性、持久性和安全性，已成为首要的基因治疗载体。在此，我们展示了在作为一个整体进行包装的复杂AAV文库中存在广泛的嵌合现象，表现为普遍的条形码交换。观察到的嵌合现象取决于长度和同源性，但与衣壳无关，在某些情况下会影响大多数包装的AAV基因组。这些结果对研究和临床环境中功能性AAV文库的设计和应用具有启示意义。
