Evidence map›Paper›PMID 33712599›Full record

ArticleNature communications2021

Adeno-associated virus capsid assembly is divergent and stochastic.

Tobias P Wörner, Antonette Bennett, Sana Habka, Joost Snijder, Olga Friese, Thomas Powers, Mavis Agbandje-McKenna, Albert J R Heck

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed
24.9field-weighted citation impact, top 1% 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

131 citing papers in PubMed, 205 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  20. Review

71 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 2 countries.

Tobias P WörnerBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, The Netherlands.
Antonette BennettDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, the McKnight Brain Institute, 1200 Newell Drive, Gainesville, FL, USA.
Sana HabkaBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, The Netherlands.
Joost SnijderBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, The Netherlands.
Olga FrieseBiotherapeutics Pharmaceutical Sciences, Pfizer WRDM, 700 Chesterfield Parkway W, Gainesville, MO, USA.
Thomas PowersBiotherapeutics Pharmaceutical Sciences, Pfizer WRDM, 700 Chesterfield Parkway W, Gainesville, MO, USA.
Mavis Agbandje-McKennaDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, the McKnight Brain Institute, 1200 Newell Drive, Gainesville, FL, USA.
Albert J R HeckBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, The Netherlands. A.J.R.Heck@uu.nl.ORCID 0000-0002-2405-4404
Utrecht University · NLAllen Institute for Brain Science · USPfizer (United States) · US

Funding

The role of pH and protease activity in AAV viral transductionR01GM109524 · NIGMS · UNIVERSITY OF FLORIDA · PI AGBANDJE-MCKENNA, MAVIS, MCKENNA, ROBERT · 2014 to 2017
$2.0M
NIGMS NIH HHS R01 GM109524
6 · The paper itself

Abstract

Adeno-associated viruses (AAVs) are increasingly used as gene therapy vectors. AAVs package their genome in a non-enveloped T = 1 icosahedral capsid of ~3.8 megaDalton, consisting of 60 subunits of 3 distinct viral proteins (VPs), which vary only in their N-terminus. While all three VPs play a role in cell-entry and transduction, their precise stoichiometry and structural organization in the capsid has remained elusive. Here we investigate the composition of several AAV serotypes by high-resolution native mass spectrometry. Our data reveal that the capsids assemble stochastically, leading to a highly heterogeneous population of capsids of variable composition, whereby even the single-most abundant VP stoichiometry represents only a small percentage of the total AAV population. We estimate that virtually every AAV capsid in a particular preparation has a unique composition. The systematic scoring of the simulations against experimental native MS data offers a sensitive new method to characterize these therapeutically important heterogeneous capsids.

Indexed as

AnimalsCapsidCapsid ProteinsDependovirusHEK293 CellsHumansSerogroupSf9 CellsViral ProteinsVirus AssemblyCapsid ProteinsViral Proteins

Identifiers

PMID33712599
PMCPMC7955066
OpenAlexW3134311741

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.