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    AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems

    Year: 2019

    Journal: Mol. Ther.-Nucl. Acids, Volume 18, DEC 6, page 432–443

    Authors: Kim, Seung-Hyun; Lee, Slgirim; Lee, Heehyung; Cho, Mira; Schaffer, David V.; Jang, Jae-Hyung

    Organizations: Basic Research Lab Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT (MSIT) [2018025230]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT (MSIT) [NRF2018R1A2A2A05020786]; Bio & Medical Technology Development Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT (MSIT) [NRF-2017M3A9B4061968, 2018M3A9H2019045, 2019M3A9H1032791]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01EY022975]; Gilbert Family Foundation [563766]

    Interfacing gene delivery vehicles with biomaterials has the potential to play a key role in diversifying gene transfer capabilities, including localized, patterned, and controlled delivery. However, strategies for modifying biomaterials to interact with delivery vectors must be redesigned whenever new delivery vehicles and applications are explored. We have developed a vector-independent biomaterial platform capable of interacting with various adeno-associated viral (AAV) serotypes. A water-soluble, cysteine-tagged, recombinant protein version of the recently discovered multi-AAV serotype receptor (AAVR), referred to as cys-AAVR, was conjugated to maleimide-displaying polycaprolactone (PCL) materials using click chemistry. The resulting cys-AAVR-PCL system bound to a broad range of therapeutically relevant AAV serotypes, thereby providing a platform capable of modulating the delivery of all AAV serotypes. Intramuscular injection of cys-AAVR-PCL microspheres with bound AAV vectors resulted in localized and sustained gene delivery as well as reduced spread to off-target organs compared to a vector solution. This cys-AAVR-PCL system is thus an effective approach for biomaterial-based AAV gene delivery for a broad range of therapeutic applications.
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