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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月28日

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  • Jean-Benoît Lalanne,
  • Chau Huynh,
  • John K. Mich,
  • Avery C. Hunker,
  • Troy A. McDiarmid,
  • Haedong Kim,
  • Boaz P. Levi,
  • Jonathan T. Ting,
  • Jay Shendure

摘要

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.