AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119302628 |
| _version_ | 1819265540889247744 |
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| author | Seung-Hyun Kim Slgirim Lee Heehyung Lee Mira Cho David V. Schaffer Jae-Hyung Jang |
| author_facet | Seung-Hyun Kim Slgirim Lee Heehyung Lee Mira Cho David V. Schaffer Jae-Hyung Jang |
| author_sort | Seung-Hyun Kim |
| collection | DOAJ |
| description | 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: adeno-associated virus, AAVR, localized gene delivery, sustained gene delivery, controlled gene delivery |
| first_indexed | 2024-12-23T20:47:01Z |
| format | Article |
| id | doaj.art-c81580fbc60145aaa290c025a95b2d5b |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-23T20:47:01Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-c81580fbc60145aaa290c025a95b2d5b2022-12-21T17:31:46ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-12-0118432443AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery SystemsSeung-Hyun Kim0Slgirim Lee1Heehyung Lee2Mira Cho3David V. Schaffer4Jae-Hyung Jang5Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, KoreaDepartment of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Korea; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USADepartment of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, KoreaDepartment of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, KoreaDepartment 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; Corresponding author: David V. Schaffer, Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720-3220.Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Korea; Corresponding author: Jae-Hyung Jang, Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Korea.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: adeno-associated virus, AAVR, localized gene delivery, sustained gene delivery, controlled gene deliveryhttp://www.sciencedirect.com/science/article/pii/S2162253119302628 |
| spellingShingle | Seung-Hyun Kim Slgirim Lee Heehyung Lee Mira Cho David V. Schaffer Jae-Hyung Jang AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems Molecular Therapy: Nucleic Acids |
| title | AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems |
| title_full | AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems |
| title_fullStr | AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems |
| title_full_unstemmed | AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems |
| title_short | AAVR-Displaying Interfaces: Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems |
| title_sort | aavr displaying interfaces serotype independent adeno associated virus capture and local delivery systems |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119302628 |
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