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

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

doi:10.1016/j.omtn.2019.09.015

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

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

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	432-443
Number of pages	12
Journal	Molecular Therapy - Nucleic Acids
Volume	18
DOIs	https://doi.org/10.1016/j.omtn.2019.09.015
Publication status	Published - 2019 Dec 6

Bibliographical note

Funding Information:
We would like to thank Dr. Jorge Santiago-Ortiz and Olivia Scheideler for their help in producing the cys-AAVR protein. This research was supported by the Basic Research Lab Program (grant no. 2018025230 ), Basic Science Research Program ( NRF-2018R1A2A2A05020786 ), and Bio & Medical Technology Development Program ( NRF-2017M3A9B4061968 , 2018M3A9H2019045 , and 2019M3A9H1032791 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT). D.S. was supported by NIH grant R01EY022975 . This work was also funded by award 563766 from the Gilbert Family Foundation .

All Science Journal Classification (ASJC) codes

Molecular Medicine
Drug Discovery

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@article{34ec92589996455b96761420080f2a6b,

title = "AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems",

abstract = "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.",

author = "Kim, {Seung Hyun} and Slgirim Lee and Heehyung Lee and Mira Cho and Schaffer, {David V.} and Jang, {Jae Hyung}",

note = "Funding Information: We would like to thank Dr. Jorge Santiago-Ortiz and Olivia Scheideler for their help in producing the cys-AAVR protein. This research was supported by the Basic Research Lab Program (grant no. 2018025230 ), Basic Science Research Program ( NRF-2018R1A2A2A05020786 ), and Bio & Medical Technology Development Program ( NRF-2017M3A9B4061968 , 2018M3A9H2019045 , and 2019M3A9H1032791 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT). D.S. was supported by NIH grant R01EY022975 . This work was also funded by award 563766 from the Gilbert Family Foundation . ",

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doi = "10.1016/j.omtn.2019.09.015",

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AU - Cho, Mira

AU - Schaffer, David V.

AU - Jang, Jae Hyung

N1 - Funding Information: We would like to thank Dr. Jorge Santiago-Ortiz and Olivia Scheideler for their help in producing the cys-AAVR protein. This research was supported by the Basic Research Lab Program (grant no. 2018025230 ), Basic Science Research Program ( NRF-2018R1A2A2A05020786 ), and Bio & Medical Technology Development Program ( NRF-2017M3A9B4061968 , 2018M3A9H2019045 , and 2019M3A9H1032791 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT). D.S. was supported by NIH grant R01EY022975 . This work was also funded by award 563766 from the Gilbert Family Foundation .

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N2 - 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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