Evidence map›Paper›PMID 34232726›Full record

ArticleJournal of virology2021

Receptor Switching in Newly Evolved Adeno-associated Viruses.

L Patrick Havlik, Anshuman Das, Mario Mietzsch, Daniel K Oh, Jonathan Ark, Robert McKenna, Mavis Agbandje-McKenna, Aravind Asokan

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  5. Article
  6. Review
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  9. Development of CNS tropic AAV1-like variants with reduced liver-targeting following systemic administration in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
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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 1 country.

L Patrick Havlik *Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
Anshuman Das *Department of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.
Mario MietzschDepartment of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.
Daniel K OhCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
Jonathan ArkCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
Robert McKennaDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, University of Floridagrid.15276.37, Gainesville, Florida, USA.ORCID 0000-0002-2792-935X
Mavis Agbandje-McKennaDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, University of Floridagrid.15276.37, Gainesville, Florida, USA.ORCID 0000-0003-0565-5578
Aravind AsokanDepartment of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.ORCID 0000-0001-5563-4877
Duke University · USUniversity of North Carolina at Chapel Hill · USUniversity of Florida · US

Funding

Determinants of AAV TropismR01HL089221 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Aravind Asokan · 2009 to 2026
$8.1M
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
Evolving High Potency AAV Vectors for Neuromuscular Genome EditingUG3AR075336 · NIAMS · DUKE UNIVERSITY · PI ASOKAN, ARAVIND · 2018 to 2020
$2.1M
RE-ENGINEERING AAV GENOME PACKAGINGR01GM127708 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ASOKAN, ARAVIND · 2018 to 2021
$2.0M
CircRNAs and CNS Gene TransferR01NS099371 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ASOKAN, ARAVIND · 2017 to 2021
$1.9M
HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL089221HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) UG3AR075336HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM082946HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM127708HHS | NIH | National Institute of General Medical Sciences (NIGMS) U21GM116792HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS099371NHLBI NIH HHS R01 HL089221NIAMS NIH HHS UG3 AR075336NIGMS NIH HHS R01 GM082946NIGMS NIH HHS R01 GM127708NIGMS NIH HHS U24 GM116788NIGMS NIH HHS U24 GM116792NINDS NIH HHS R01 NS099371
6 · The paper itself

Abstract

Adeno-associated viruses utilize different glycans and the AAV receptor (AAVR) for cellular attachment and entry. Directed evolution has yielded new AAV variants; however, structure-function correlates underlying their improved transduction are generally overlooked. Here, we report that infectious cycling of structurally diverse AAV surface loop libraries yields functionally distinct variants. Newly evolved variants show enhanced cellular binding, uptake, and transduction, but through distinct mechanisms. Using glycan-based and genome-wide CRISPR knockout screens, we discover that one AAV variant acquires the ability to recognize sulfated glycosaminoglycans, while another displays receptor switching from AAVR to integrin β1 (ITGB1). A previously evolved variant, AAVhum.8, preferentially utilizes the ITGB1 receptor over AAVR. Visualization of the AAVhum.8 capsid by cryoelectron microscopy at 2.49-Å resolution localizes the newly acquired integrin recognition motif adjacent to the AAVR footprint. These observations underscore the new finding that distinct AAV surface epitopes can be evolved to exploit different cellular receptors for enhanced transduction.

Indexed as

Directed Molecular EvolutionAmino Acid MotifsCapsidCapsid ProteinsCell LineCell MembraneCRISPR-Cas SystemsCryoelectron MicroscopyDependovirusGenetic VariationGlycosaminoglycansHumansIntegrin beta1PolysaccharidesReceptors, Cell SurfaceReceptors, VirusA73025Capsid ProteinsGlycosaminoglycansIntegrin beta1Itgb1 protein, humanKIAA0319L protein, humanPolysaccharidesReceptors, Cell SurfaceReceptors, Virusadeno-associated viruscapsidCRISPRcryo-EMgene therapyreceptorstructure-function

Identifiers

PMID34232726
PMCPMC8428401
OpenAlexW3178816563

What OpenQuestion holds

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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.