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 journalArticle

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 languageEnglish
Pages (from-to)432-443
Number of pages12
JournalMolecular Therapy - Nucleic Acids
Volume18
DOIs
Publication statusPublished - 2019 Dec 6

Fingerprint

Dependovirus
Biocompatible Materials
Click Chemistry
Genes
Viral Genes
Serogroup
Intramuscular Injections
Microspheres
Recombinant Proteins
Cysteine
polycaprolactone
Water

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Kim, Seung Hyun ; Lee, Slgirim ; Lee, Heehyung ; Cho, Mira ; Schaffer, David V. ; Jang, Jae Hyung. / AAVR-Displaying Interfaces : Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems. In: Molecular Therapy - Nucleic Acids. 2019 ; Vol. 18. pp. 432-443.
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AAVR-Displaying Interfaces : Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems. / Kim, Seung Hyun; Lee, Slgirim; Lee, Heehyung; Cho, Mira; Schaffer, David V.; Jang, Jae Hyung.

In: Molecular Therapy - Nucleic Acids, Vol. 18, 06.12.2019, p. 432-443.

Research output: Contribution to journalArticle

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