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 | |
| Publication status | Published - 2019 Dec 6 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery
Cite this
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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 journal › Article
TY - JOUR
T1 - AAVR-Displaying Interfaces
T2 - Serotype-Independent Adeno-Associated Virus Capture and Local Delivery Systems
AU - Kim, Seung Hyun
AU - Lee, Slgirim
AU - Lee, Heehyung
AU - Cho, Mira
AU - Schaffer, David V.
AU - Jang, Jae Hyung
PY - 2019/12/6
Y1 - 2019/12/6
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85073684868&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073684868&partnerID=8YFLogxK
U2 - 10.1016/j.omtn.2019.09.015
DO - 10.1016/j.omtn.2019.09.015
M3 - Article
AN - SCOPUS:85073684868
VL - 18
SP - 432
EP - 443
JO - Molecular Therapy - Nucleic Acids
JF - Molecular Therapy - Nucleic Acids
SN - 2162-2531
ER -