Figure 1.

Development of NextGen AAV vectors. Surface-exposed, specific tyrosine, serine, and threonine residues on AAV capsids can be phosphorylated, which is a signal for ubiquitination. Similarly, surface-exposed, specific lysine residues on AAV capsids can be ubiquitinated, and subsequently degraded by the host cell proteasome machinery. Site-directed mutagenesis of these residues led to the generation of NextGen AAV vectors that circumvent these problems, and are more efficient at reduced vector doses, thus minimizing host immune responses.