Zinn, E. et al. Cell Rep. 12, 1056–1068 (2015).

Adeno-associated virus vectors (AAVs) have been widely used for gene delivery in basic research, and they have also been explored for therapeutic purposes. However, their utility depends on target-tissue specificity and tolerance by the immune system. To expand the potential pool of AAV types, Zinn et al. used an in silico approach to determine putative ancestral AAVs. Using ancestral sequence reconstruction, they were able to predict AAV variants that adhered to the strict structural and functional requirements of AAVs. The researchers synthesized one of the ancestral AAVs, Anc80L65, and showed that it could infect mouse liver, muscle and retina, without eliciting a major immune response. In addition, Anc80L65 was able to mediate efficient gene transfer into macaque liver.