Fig. 1.

Molecular engineering and evolution approaches have been applied to design AAV viral vectors for tropism change (A–D) and evasion of neutralizing antibodies (NABs) (C–F). A Mosaic capsids, composed of a mixture of capsid subunits from different serotypes, can possess the beneficial features of different serotypes. B Decoration of AAV capsids with either an antibody or a peptide targeting a cellular receptor can yield a targeted vector. C Pseudotyping the AAV2 genome with a capsid from a different serotype can “transfer” the desirable properties of the different serotype to AAV2. D Directed evolution of the AAV capsid, distinct from single round library generation and selection, involves multiple rounds of genetic diversification and selection. AAV libraries containing capsid variants are generated and subjected to selection for novel, diverse properties. Specific variants with desirable properties will be enriched and used for library generation of a next round of selection (denoted by the solid, curved arrows). E Disruption of the epitopes of AAV2 NABs allows evasion of antibody neutralization. F Conjugation of a synthetic polymer to AAV capsid can shield the AAV vector from NABs.