OCA at 13:00, 13 October 2021

OCA — Wed, 13 Oct 2021 13:00:18 GMT

←Older revision		Revision as of 13:00, 13 October 2021
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	==The AAVrh.10-glycan complex==		==The AAVrh.10-glycan complex==
-	<StructureSection load='7s1w' size='340' side='right'caption='[[7s1w]]' scene=''>	+	<StructureSection load='7s1w' size='340' side='right'caption='[[7s1w]], [[Resolution\|resolution]] 3.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S1W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7s1w]] is a 60 chain structure with sequence from [https://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=7S1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S1W FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7s1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s1w OCA], [https://pdbe.org/7s1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s1w RCSB], [https://www.ebi.ac.uk/pdbsum/7s1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s1w ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7s1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s1w OCA], [https://pdbe.org/7s1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s1w RCSB], [https://www.ebi.ac.uk/pdbsum/7s1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s1w ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Recombinant Adeno-associated virus (rAAV) vectors are one of the leading tools for the delivery of therapeutic genes in human gene therapy applications. For a successful transfer of their payload, the AAV vectors have to circumvent potential pre-existing neutralizing host antibodies and bind to the receptor of the target cells. Both these aspects have not been structurally analyzed for AAVrh.10. Here, cryo-electron microscopy (cryo-EM) and three-dimensional image reconstruction were used to map the binding site of sulfated N-Acetyllactosamine (LacNAc, previously shown to bind AAVrh.10) and a series of four monoclonal antibodies (MAbs). LacNAc was found to bind to a pocket located on the side of the 3-fold capsid protrusion, that is mostly conserved to AAV9 and equivalent to its galactose-binding site. As a result, AAVrh.10 was also shown to be able to bind to cell surface glycans with terminal galactose. For the antigenic characterization, it was observed that several anti-AAV8 MAbs cross-react with AAVrh.10. The binding sites of these antibodies were mapped to the 3-fold capsid protrusions. Based on these observations, the AAVrh.10 capsid surface was engineered to create variant capsids that escape these antibodies while maintaining infectivity. Importance Gene therapy vectors based on Adeno-associated virus rhesus isolate 10 (AAVrh.10) have been used in several clinical trials to treat monogenetic diseases. However, compared to other AAV serotypes little is known about receptor binding and antigenicity of the AAVrh.10 capsid. Particularly, pre-existing neutralizing antibodies against capsids are an important challenge that can hamper treatment efficiency. This study addresses both topics and identifies critical regions of the AAVrh.10 capsid for receptor and antibody binding. The insights gained were utilized to generate AAVrh.10 variants capable of evading known neutralizing antibodies. The findings of this study could further aid the utilization of AAVrh.10 vectors in clinical trials and help the approval of the subsequent biologics.
		+
		+	Structural study of AAVrh.10 Receptor and Antibody Interactions.,Mietzsch M, Yu JC, Hsi J, Chipman P, Broecker F, Fuming Z, Linhardt RJ, Seeberger PH, Heilbronn R, McKenna R, Agbandje-McKenna M J Virol. 2021 Sep 22:JVI0124921. doi: 10.1128/JVI.01249-21. PMID:34549984<ref>PMID:34549984</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7s1w" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Adeno-associated virus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: McKenna R]]	+	[[Category: McKenna, R]]
-	[[Category: Mietzsch M]]	+	[[Category: Mietzsch, M]]
		+	[[Category: Aavrh 10]]
		+	[[Category: Capsid]]
		+	[[Category: Galactose]]
		+	[[Category: Glycan complex]]
		+	[[Category: Lacnac]]
		+	[[Category: Virus]]

OCA at 06:53, 22 September 2021

OCA — Wed, 22 Sep 2021 06:53:45 GMT

←Older revision		Revision as of 06:53, 22 September 2021
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-	'''Unreleased structure'''

-	The ~~entry~~ 7s1w ~~is ON HOLD~~	+	==The AAVrh.10-glycan complex==
-		+	<StructureSection load='7s1w' size='340' side='right'caption='[[7s1w]]' scene=''>
-	~~Authors~~: ~~Mietzsch~~, M., ~~McKenna~~, R.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S1W FirstGlance]. <br>
-	~~Description~~: ~~The AAVrh~~.10-~~glycan complex~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7s1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s1w OCA], [https://pdbe.org/7s1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s1w RCSB], [https://www.ebi.ac.uk/pdbsum/7s1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s1w ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Mckenna,~~ R]]	+	__TOC__
-	[[Category: Mietzsch, M]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: McKenna R]]
		+	[[Category: Mietzsch M]]

OCA: Protected "7s1w" [edit=sysop:move=sysop]

OCA — Wed, 08 Sep 2021 07:53:59 GMT

Protected "7s1w" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:53, 8 September 2021

OCA: New page: '''Unreleased structure''' The entry 7s1w is ON HOLD Authors: Mietzsch, M., McKenna, R. Description: The AAVrh.10-glycan complex Category: Unreleased Structures [[Category: Mckenna...

OCA — Wed, 08 Sep 2021 07:53:58 GMT

New page: '''Unreleased structure''' The entry 7s1w is ON HOLD Authors: Mietzsch, M., McKenna, R. Description: The AAVrh.10-glycan complex Category: Unreleased Structures [[Category: Mckenna...

New page

'''Unreleased structure'''

The entry 7s1w is ON HOLD

Authors: Mietzsch, M., McKenna, R.

Description: The AAVrh.10-glycan complex
[[Category: Unreleased Structures]]
[[Category: Mckenna, R]]
[[Category: Mietzsch, M]]

7s1w - Revision history

OCA at 13:00, 13 October 2021

OCA at 06:53, 22 September 2021

OCA: Protected "7s1w" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7s1w is ON HOLD Authors: Mietzsch, M., McKenna, R. Description: The AAVrh.10-glycan complex Category: Unreleased Structures [[Category: Mckenna...