Site-Specific Post-translational Surface Modification of Adeno-Associated Virus Vectors Using Leucine Zippers.

ABSTRACT: Adeno-associated virus (AAV) is widely favored as a gene therapy vector, tested in over 200 clinical trials internationally. To improve targeted delivery a variety of genetic capsid modifications, such as insertion of targeting proteins/peptides into the capsid shell, have been explored with some success but larger insertions often have unpredictable deleterious impacts on capsid formation and gene delivery. Here, we demonstrate a modular platform for the integration of exogenous peptides and proteins onto the AAV capsid post-translationally while preserving vector functionality. We decorated the AAV capsid with leucine-zipper coiled-coil binding motifs that exhibit specific noncovalent heterodimerization. AAV capsids successfully display hexahistidine tagged-peptides using this approach,

SUBMITTER: Thadani NN 

PROVIDER: S-EPMC7323921 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature