Evidence map›Paper›PMID 31859208›Full record

ArticleJournal of structural biology2020

Structure comparison of the chimeric AAV2.7m8 vector with parental AAV2.

Antonette Bennett, Annahita Keravala, Victoria Makal, Justin Kurian, Brahim Belbellaa, Rangoli Aeran, Yu-Shan Tseng, Duncan Sousa, John Spear, Mehdi Gasmi and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of structural biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  3. Gene Therapy for Wet Age-Related Macular Degeneration.Bioengineering (Basel, Switzerland) · 2025
    Review
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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

11 authors at 3 institutions in 1 country.

Antonette BennettDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA.
Annahita KeravalaAdverum Biotechnologies, 1035 O'Brien Dr., Menlo Park, CA 94025, USA.
Victoria MakalDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA.
Justin KurianDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA.
Brahim BelbellaaAdverum Biotechnologies, 1035 O'Brien Dr., Menlo Park, CA 94025, USA.
Rangoli AeranAdverum Biotechnologies, 1035 O'Brien Dr., Menlo Park, CA 94025, USA.
Yu-Shan TsengAdverum Biotechnologies, 1035 O'Brien Dr., Menlo Park, CA 94025, USA.
Duncan SousaBiological Science Imaging Resource, Department of Biological Sciences, The Florida State University, 89 Chieftan Way, Rm 119, Tallahassee, FL 32306, USA.
John SpearBiological Science Imaging Resource, Department of Biological Sciences, The Florida State University, 89 Chieftan Way, Rm 119, Tallahassee, FL 32306, USA.
Mehdi GasmiAdverum Biotechnologies, 1035 O'Brien Dr., Menlo Park, CA 94025, USA. Electronic address: mehdi@adverum.com.
Mavis Agbandje-McKennaDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA. Electronic address: mckenna@ufl.edu.
University of Florida · USFlorida State University · USATUM (United States) · 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
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
Purchase of a direct electron camera for the Titan-Krios at FSUS10OD018142 · OD · FLORIDA STATE UNIVERSITY · PI TAYLOR, KENNETH ALLEN · 2014 to 2014
$384k
NCRR NIH HHS S10 RR025080NIGMS NIH HHS R01 GM082946NIGMS NIH HHS R01 GM109524NIGMS NIH HHS U24 GM116788NIGMS NIH HHS U24 GM116792NIH HHS S10 OD018142
6 · The paper itself

Abstract

The AAV2.7m8 vector is an engineered capsid with a 10-amino acid insertion in adeno-associated virus (AAV) surface variable region VIII (VR-VIII) resulting in the alteration of an antigenic region of AAV2 and the ability to efficiently transduce retina cells following intravitreal administration. Directed evolution and in vivo screening in the mouse retina isolated this vector. In the present study, we sought to identify the structural differences between a recombinant AAV2.7m8 (rAAV2.7m8) vector packaging a GFP genome and its parental serotype, AAV2, by cryo-electron microscopy (cryo-EM) and image reconstruction. The structures of rAAV2.7m8 and AAV2 were determined to 2.91 and 3.02 Å resolution, respectively. The rAAV2.7m8 amino acid side-chains for residues 219-745 (the last C-terminal residue) were interpretable in the density map with the exception of the 10 inserted amino acids. While observable in a low sigma threshold density, side-chains were only resolved at the base of the insertion, likely due to flexibility at the top of the loop. A comparison to parental AAV2 (ordered from residues 217-735) showed the structures to be similar, except at some side-chains that had different orientations and, in VR-VIII containing the 10 amino acid insertion. VR-VIII is part of an AAV2 antigenic epitope, and the difference is consistent with rAAV2.7m8's escape from a known AAV2 monoclonal antibody, C37-B. The observations provide valuable insight into the configuration of inserted surface peptides on the AAV capsid and structural differences to be leveraged for future AAV vector rational design, especially for retargeted tropism and antibody escape.

Indexed as

AnimalsCapsidCryoelectron MicroscopyDependovirusGenetic VectorsHumansMiceParvovirinaeAAVAAV2.7m8Adeno-associated viruscryo-EMGene delivery

Identifiers

PMID31859208
PMCPMC7058502
OpenAlexW2996414279

What OpenQuestion holds

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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.