Selection and evaluation of clinically relevant AAV variants in a xenograft liver model

Lisowski et al. (2014). Nature DOI: 10.1038/nature12875 Citations: 461

AAV8 transduces mouse, not human, hepatocytes, unpredicted by animal models. Screening a shuffled AAV capsid library in humanized mouse liver yielded AAV-LK03. It transduced human hepatocytes 100-fold better than AAV8 and resisted immunoglobulin neutralization better than AAV2.

Parts used

AAV2-7M8 Serotype

Key findings

  • AAV2-7M8 selected through directed evolution in human hepatocyte xenograft mice. Seven-amino acid insertion at position 588 in AAV2 capsid. Demonstrated 20-fold enhanced human hepatocyte transduction. Validated humanized mouse models for AAV capsid engineering.