Multiparametric domain insertional profiling of adeno-associated virus VP1.

Several evolved properties of adeno-associated virus (AAV), such as broad tropism and immunogenicity in humans, are barriers to AAV-based gene therapy. Most efforts to re-engineer these properties have focused on variable regions near AAV's 3-fold protrusions and capsid protein termini. To comprehensively survey AAV capsids for engineerable hotspots, we determined multiple AAV fitness phenotypes upon insertion of six structured protein domains into the entire AAV-DJ capsid protein VP1.

Multiparametric domain insertional profiling of Adeno-Associated Virus VP1.

Evolved properties of Adeno-Associated Virus (AAV), such as broad tropism and immunogenicity in humans, are barriers to AAV-based gene therapy. Previous efforts to re-engineer these properties have focused on variable regions near AAV’s 3-fold protrusions and capsid protein termini. To comprehensively survey AAV capsids for engineerable hotspots, we determined multiple AAV fitness phenotypes upon insertion of large, structured protein domains into the entire AAV-DJ capsid protein VP1.

Programmable Assembly of Adeno-Associated Virus-Antibody Composites for Receptor-Mediated Gene Delivery.

Adeno-associated virus (AAV) has emerged as a viral gene delivery vector that is safe in humans, able to infect both dividing and arrested cells and drive long-term expression (>6 months). Unfortunately, the naturally evolved properties of many AAV serotypes-including low cell type specificity and largely overlapping tropism-are mismatched to applications that require cell type-specific infection, such as neural circuit mapping or precision gene therapy. A variety of approaches to redirect AAV tropism exist, but there is still the need for a universal solution for directing AAV tropism toward user-defined cellular receptors that does not require extensive case-by-case optimization and works with readily available components.