Evidence map›Paper›PMID 35532224›Full record

ArticleJournal of virology2022

Characterization of the Serpentine Adeno-Associated Virus (SAAV) Capsid Structure: Receptor Interactions and Antigenicity.

Mario Mietzsch, Joshua A Hull, Victoria E Makal, Alberto Jimenez Ybargollin, Jennifer C Yu, Kedrick McKissock, Antonette Bennett, Judit Penzes, Bridget Lins-Austin, Qian Yu and 7 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. The Structure ofViruses · 2024
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Mario MietzschUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Joshua A HullUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Victoria E MakalUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Alberto Jimenez YbargollinUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Jennifer C YuUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Kedrick McKissockUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Antonette BennettUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Judit PenzesUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Bridget Lins-AustinUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Qian YuNRS-Institut Armand Frappier, Université du Québec, Laval, Quebec, Canada.
Paul ChipmanUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.
Nilakshee BhattacharyaBiological Science Imaging Resource, Department of Biological Sciences, Florida State Universitygrid.255986.5, Tallahassee, Florida, USA.
Duncan SousaBiological Science Imaging Resource, Department of Biological Sciences, Florida State Universitygrid.255986.5, Tallahassee, Florida, USA.
David StrugatskyDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Peter TijssenNRS-Institut Armand Frappier, Université du Québec, Laval, Quebec, Canada.
Robert McKennaUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.ORCID 0000-0002-2792-935X
Mavis Agbandje-McKennaUniversity of Floridagrid.15276.37, Department of Biochemistry & Molecular Biology, Gainesville, Florida, USA.ORCID 0000-0003-0565-5578
University of Florida · USFlorida State University · USInstitut National de la Recherche Scientifique · CAUniversity of California, Los Angeles · US

Funding

Structural studies of AAV capsids and their glycan receptor interactionsR01GM082946 · NIGMS · UNIVERSITY OF FLORIDA · PI ROBERT MCKENNA · 2007 to 2026
$6.1M
The Southeastern Consortium for Microscopy of MacroMolecular MachinesU24GM116788 · NIGMS · FLORIDA STATE UNIVERSITY · PI AGBANDJE-MCKENNA, MAVIS, BULLITT, ESTHER · 2016 to 2020
$4.6M
West/Midwest Consortium for High-Resolution Cryo Electron MicroscopyU24GM116792 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGBANDJE-MCKENNA, MAVIS, DOKLAND, TERJE · 2016 to 2020
$3.0M
Purchase of a FEI Titan Krios for 3-D EMS10RR025080 · NCRR · FLORIDA STATE UNIVERSITY · PI TAYLOR, KENNETH ALLEN · 2008 to 2008
$2.0M
HIGH-END CRYOEM INSTRUMENT FOR UCLA ELECTRON IMAGING CTR FOR NANOMACHINES: AIDSS10RR023057 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHOU, Z HONG · 2006 to 2006
$1.6M
Direct Detection Device for atomic resolution cryoEM of macromolecular complexesS10OD018111 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHOU, Z HONG · 2014 to 2014
$598k
Purchase of a direct electron camera for the Titan-Krios at FSUS10OD018142 · OD · FLORIDA STATE UNIVERSITY · PI TAYLOR, KENNETH ALLEN · 2014 to 2014
$384k
HHS | National Institutes of Health (NIH) GM082946NCRR NIH HHS S10 RR023057NCRR NIH HHS S10 RR025080NIGMS NIH HHS R01 GM082946NIGMS NIH HHS U24 GM116788NIGMS NIH HHS U24 GM116792NIH HHS S10 OD018111NIH HHS S10 OD018142
6 · The paper itself

Abstract

Adeno-associated viruses (AAVs) are being developed as clinical gene therapy vectors. One issue undermining their broad use in the clinical setting is the high prevalence of circulating antibodies in the general population capable of neutralizing AAV vectors. Hence, there is a need for AAV vectors that can evade the preexisting immune response. One possible source of human naive vectors are AAVs that do not disseminate in the primate population, and one such example is serpentine AAV (SAAV). This study characterizes the structural and biophysical properties of the SAAV capsid and its receptor interactions and antigenicity. Single particle cryo-electron microscopy (cryo-EM) and thermal stability studies were conducted to characterize the SAAV capsid structure at pH 7.4, 6.0, 5.5, and 4.0, conditions experienced during cellular trafficking. Cell binding assays using Chinese hamster ovary (CHO) cell lines identified terminal sialic acid as the primary attachment receptor for SAAV similar to AAV1, 4, 5, and 6. The binding site of sialic acid to the SAAV capsid was mapped near the 2-fold axis toward the 2/5-fold wall, in a different location than AAV1, 4, 5, and 6. Towards determining the SAAV capsid antigenicity native immunodot blots showed that SAAV evades AAV serotype-specific mouse monoclonal antibodies. However, despite its reptilian origin, it was recognized by ~25% of 50 human sera tested, likely due to the presence of cross-reactive antibodies. These findings will inform future gene delivery applications using SAAV-based vectors and further aid the structural characterization and annotation of the repertoire of available AAV capsids.

Indexed as

CapsidDependovirusAnimalsCapsid ProteinsCHO CellsCricetinaeCricetulusCross ReactionsCryoelectron MicroscopyEpitopesGenetic VectorsHumansModels, MolecularN-Acetylneuraminic AcidCapsid ProteinsEpitopesN-Acetylneuraminic AcidAAVadeno-associated virusantibodycapsidcryo-EMgene therapyhuman seraparvovirusreceptorsialic acid

Identifiers

PMID35532224
PMCPMC9175632
OpenAlexW4229372493

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.