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

Mol Ther Nucleic Acids. 2019 Dec 6:18:432-443. doi: 10.1016/j.omtn.2019.09.015. Epub 2019 Sep 24.

Authors

Seung-Hyun Kim¹, Slgirim Lee², Heehyung Lee¹, Mira Cho¹, David V Schaffer³, Jae-Hyung Jang⁴

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Korea.
² Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Korea; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA.
³ Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720-3220, USA; Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720-3220, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720-3220, USA. Electronic address: schaffer@berkeley.edu.
⁴ Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Korea. Electronic address: j-jang@yonsei.ac.kr.

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.

Keywords: AAVR; adeno-associated virus; controlled gene delivery; localized gene delivery; sustained gene delivery.

Grants and funding

R01 EY022975/EY/NEI NIH HHS/United States