4iov: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==The structure of AAVrh32.33, a Novel Gene Delivery Vector== | |||
===The structure of AAVrh32.33, a | <StructureSection load='4iov' size='340' side='right' caption='[[4iov]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4iov]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Adeno-associated_virus Adeno-associated virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IOV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IOV FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D5M:2-DEOXYADENOSINE-5-MONOPHOSPHATE'>D5M</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Adeno associated virus Rh32-33 VP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272636 Adeno-associated virus])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4iov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iov OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iov RCSB], [http://www.ebi.ac.uk/pdbsum/4iov PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Adeno-associated viruses (AAVs) are being developed as gene delivery vectors for therapeutic clinical applications. However, the host antibody immune response directed against their capsid, prevalent in approximately 40-70% of the general population, depending on serotype, negatively impacts efficacy. AAVrh32.33, a novel vector developed from rhesus macaques isolates, has significantly lower seroprevalence in human populations compared to AAV2 and AAV8, which are both in clinical use. To better understand the capsid determinants of this differential immune response to AAVrh32.33, its structure was determined by X-ray crystallography to 3.5A resolution. The capsid viral protein (VP) structure conserves the eight-stranded beta-barrel core and alphaA helix reported for other parvoviruses and the distinct capsid surface topology of the AAVs: a depression at the icosahedral twofold axis, three protrusions surrounding the threefold axis, and a depression surround a cylindrical channel at the fivefold axis. A comparison to AAV2, AAV4, and AAV8, to which AAVrh32.33 shares approximately 61%, approximately 81%, and approximately 63% identity, respectively, identified differences in previously defined AAV VP structurally variable regions (VR-1 to VR-IX) which function as receptor attachment, transduction efficiency, and/or antigenic determinants. This structure thus provides a 3D platform for capsid engineering in ongoing efforts to develop AAVrh32.33, as well as other AAV serotypes, for tissue targeted gene-therapy applications with vectors that can evade pre-existing antibody responses against the capsid. These features are required for full clinical realization of the promising AAV gene delivery system. | |||
The structure of AAVrh32.33, a novel gene delivery vector.,Mikals K, Nam HJ, Van Vliet K, Vandenberghe LH, Mays LE, McKenna R, Wilson JM, Agbandje-McKenna M J Struct Biol. 2014 May;186(2):308-17. doi: 10.1016/j.jsb.2014.03.020. Epub 2014 , Apr 2. PMID:24704217<ref>PMID:24704217</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Adeno-associated virus]] | |||
[[Category: Agbandje-McKenna, M.]] | [[Category: Agbandje-McKenna, M.]] | ||
[[Category: Mays, L E.]] | [[Category: Mays, L E.]] | ||
Revision as of 10:06, 28 May 2014
The structure of AAVrh32.33, a Novel Gene Delivery VectorThe structure of AAVrh32.33, a Novel Gene Delivery Vector
Structural highlights
Publication Abstract from PubMedThe Adeno-associated viruses (AAVs) are being developed as gene delivery vectors for therapeutic clinical applications. However, the host antibody immune response directed against their capsid, prevalent in approximately 40-70% of the general population, depending on serotype, negatively impacts efficacy. AAVrh32.33, a novel vector developed from rhesus macaques isolates, has significantly lower seroprevalence in human populations compared to AAV2 and AAV8, which are both in clinical use. To better understand the capsid determinants of this differential immune response to AAVrh32.33, its structure was determined by X-ray crystallography to 3.5A resolution. The capsid viral protein (VP) structure conserves the eight-stranded beta-barrel core and alphaA helix reported for other parvoviruses and the distinct capsid surface topology of the AAVs: a depression at the icosahedral twofold axis, three protrusions surrounding the threefold axis, and a depression surround a cylindrical channel at the fivefold axis. A comparison to AAV2, AAV4, and AAV8, to which AAVrh32.33 shares approximately 61%, approximately 81%, and approximately 63% identity, respectively, identified differences in previously defined AAV VP structurally variable regions (VR-1 to VR-IX) which function as receptor attachment, transduction efficiency, and/or antigenic determinants. This structure thus provides a 3D platform for capsid engineering in ongoing efforts to develop AAVrh32.33, as well as other AAV serotypes, for tissue targeted gene-therapy applications with vectors that can evade pre-existing antibody responses against the capsid. These features are required for full clinical realization of the promising AAV gene delivery system. The structure of AAVrh32.33, a novel gene delivery vector.,Mikals K, Nam HJ, Van Vliet K, Vandenberghe LH, Mays LE, McKenna R, Wilson JM, Agbandje-McKenna M J Struct Biol. 2014 May;186(2):308-17. doi: 10.1016/j.jsb.2014.03.020. Epub 2014 , Apr 2. PMID:24704217[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||