dc.contributor.author |
Ussher, JE |
en |
dc.contributor.author |
Taylor, John |
en |
dc.date.accessioned |
2012-03-08T02:08:21Z |
en |
dc.date.issued |
2010 |
en |
dc.identifier.citation |
Human Gene Therapy 21(12):1675-1686 2010 |
en |
dc.identifier.issn |
1043-0342 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/13419 |
en |
dc.description.abstract |
Dendritic cells are the key antigen-presenting cells involved in the initiation of the adaptive immune response. Recombinant adeno-associated viruses (rAAVs) can transduce dendritic cells and have gained attention as potential vaccines capable of stimulating T cell immunity. Here we show that rAAV2 pseudotyped with type 6 capsid (rAAV2/6) exhibits significantly higher tropism for human monocyte-derived dendritic cells (MoDCs) than other serotypes and variants. Transduction was abolished by a single lysine-to-alanine mutation within the AAV6 capsid previously shown to inhibit binding to heparin. However, unlike rAAV2, soluble heparin did not inhibit rAAV2/6 transduction of MoDCs. Further enhancement of MoDC transduction was observed after mutation of Tyr-731 in the capsid of AAV6 consistent with a report that tyrosine residues are phosphorylated, leading to ubiquitination of capsids during uptake. Pseudotyped rAAV2/6 vectors containing a Y731F mutation minimally altered the immunophenotype of MoDCs, which retained their immunostimulatory ability and were able to stimulate an antigen-specific CD8+ T cell clone. These findings should assist in the development of rAAV2/6 as a vaccine vector. |
en |
dc.language |
EN |
en |
dc.publisher |
Mary Ann Liebert, Inc. |
en |
dc.relation.ispartofseries |
Human Gene Therapy |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from: http://www.sherpa.ac.uk/romeo/issn/1043-0342/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
HUMAN-IMMUNODEFICIENCY-VIRUS |
en |
dc.subject |
HIGH-EFFICIENCY TRANSDUCTION |
en |
dc.subject |
CD8(+) T-CELLS |
en |
dc.subject |
GENE-THERAPY |
en |
dc.subject |
ADENOVIRAL VECTOR |
en |
dc.subject |
TYROSINE RESIDUES |
en |
dc.subject |
IMMUNE-RESPONSES |
en |
dc.subject |
POINT-MUTATIONS |
en |
dc.subject |
HEPARIN-BINDING |
en |
dc.subject |
NERVOUS-SYSTEM |
en |
dc.title |
Optimized Transduction of Human Monocyte-Derived Dendritic Cells by Recombinant Adeno-Associated Virus Serotype 6 |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1089/hum.2010.087 |
en |
pubs.issue |
12 |
en |
pubs.begin-page |
1675 |
en |
pubs.volume |
21 |
en |
dc.rights.holder |
Copyright: Mary Ann Liebert, Inc. |
en |
dc.identifier.pmid |
20578847 |
en |
pubs.end-page |
1686 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
204557 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2012-02-27 |
en |
pubs.dimensions-id |
20578847 |
en |