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

ACS Synth Biol. 2020; 
Thadani NN, Yang J, Moyo B, Lee CM, Chen MY, Bao G, Suh J, , .
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摘要

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 ... More

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