6ubm: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ubm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Adeno-associated_virus_-_8 Adeno-associated virus - 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UBM FirstGlance]. <br>
<table><tr><td colspan='2'>[[6ubm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Adeno-associated_virus_-_8 Adeno-associated virus - 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UBM 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=6ubm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ubm OCA], [https://pdbe.org/6ubm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ubm RCSB], [https://www.ebi.ac.uk/pdbsum/6ubm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ubm ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</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=6ubm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ubm OCA], [https://pdbe.org/6ubm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ubm RCSB], [https://www.ebi.ac.uk/pdbsum/6ubm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ubm ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/Q8JQF8_9VIRU Q8JQF8_9VIRU]
Different approaches are used in the production of recombinant adeno-associated virus (rAAV). The two leading approaches are transiently transfected human HEK293 cells and live baculovirus infection of Spodoptera frugiperda (Sf9) insect cells. Unexplained differences in vector performance have been seen clinically and preclinically. Thus, we performed a controlled comparative production analysis varying only the host cell species but maintaining all other parameters. We characterized differences with multiple analytical approaches: proteomic profiling by mass spectrometry, isoelectric focusing, cryo-EM (transmission electron cryomicroscopy), denaturation assays, genomic and epigenomic sequencing of packaged genomes, human cytokine profiling, and functional transduction assessments in vitro and in vivo, including in humanized liver mice. Using these approaches, we have made two major discoveries: (1) rAAV capsids have post-translational modifications (PTMs), including glycosylation, acetylation, phosphorylation, and methylation, and these differ between platforms; and (2) rAAV genomes are methylated during production, and these are also differentially deposited between platforms. Our data show that host cell protein impurities differ between platforms and can have their own PTMs, including potentially immunogenic N-linked glycans. Human-produced rAAVs are more potent than baculovirus-Sf9 vectors in various cell types in vitro (p &lt; 0.05-0.0001), in various mouse tissues in vivo (p &lt; 0.03-0.0001), and in human liver in vivo (p &lt; 0.005). These differences may have clinical implications for rAAV receptor binding, trafficking, expression kinetics, expression durability, vector immunogenicity, as well as cost considerations.
 
Methods Matter: Standard Production Platforms for Recombinant AAV Produce Chemically and Functionally Distinct Vectors.,Rumachik NG, Malaker SA, Poweleit N, Maynard LH, Adams CM, Leib RD, Cirolia G, Thomas D, Stamnes S, Holt K, Sinn P, May AP, Paulk NK Mol Ther Methods Clin Dev. 2020 May 22;18:98-118. doi:, 10.1016/j.omtm.2020.05.018. eCollection 2020 Sep 11. PMID:32995354<ref>PMID:32995354</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ubm" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Adeno-associated virus - 8]]
[[Category: Adeno-associated virus - 8]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Paulk, N K]]
[[Category: Paulk NK]]
[[Category: Poweleit, N]]
[[Category: Poweleit N]]
[[Category: Aav]]
[[Category: Adeno-associated virus]]
[[Category: Capsid]]
[[Category: Gene therapy vector]]
[[Category: Post translational modification]]
[[Category: Virus]]

Latest revision as of 12:29, 20 March 2024

AAV8 Baculovirus-Sf9 produced, empty capsidAAV8 Baculovirus-Sf9 produced, empty capsid

Structural highlights

6ubm is a 1 chain structure with sequence from Adeno-associated virus - 8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8JQF8_9VIRU

See Also

6ubm, resolution 3.30Å

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