Evidence map›Paper›PMID 16378984›Full record

ArticleJournal of virology2006

Mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization.

Michael A Lochrie, Gwen P Tatsuno, Brian Christie, Jennifer Wellman McDonnell, Shangzhen Zhou, Richard Surosky, Glenn F Pierce, Peter Colosi

Open access · greenAbstract readComparative Study
In one paragraph

Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

139 citing papers in PubMed, 195 citations in OpenAlex.

  1. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2012
    Trial
  2. Article
  3. Article
  4. Review
  5. AAV capsid sites breakdown: large protein insertions impact on vector dynamics.Frontiers in bioengineering and biotechnology · 2026
    Article
  6. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  7. Review
  8. Review
  9. Targeted gene delivery systems for T-cell engineering.Cellular oncology (Dordrecht, Netherlands) · 2024
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article

79 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 2 institutions in 1 country.

Michael A LochrieAvigen, Inc., Alameda, California 94502-6541, USA.
Gwen P Tatsuno
Brian Christie
Jennifer Wellman McDonnell
Shangzhen Zhou
Richard Surosky
Glenn F Pierce
Peter Colosi
GeneTrace Systems (United States) · USEpigen Biosciences (United States) · US

Funding

Retinal Gene TherapyZIAEY000443 · NEI · NATIONAL EYE INSTITUTE · PI LI, TIANSEN · 2009 to 2020
$8.4M
Retinal Gene TherapyZ01EY000443 · NEI · NATIONAL EYE INSTITUTE · PI COLOSI, PETER · 2007 to 2008
$1.6M
6 · The paper itself

Abstract

Mutations were made at 64 positions on the external surface of the adeno-associated virus type 2 (AAV-2) capsid in regions expected to bind antibodies. The 127 mutations included 57 single alanine substitutions, 41 single nonalanine substitutions, 27 multiple mutations, and 2 insertions. Mutants were assayed for capsid synthesis, heparin binding, in vitro transduction, and binding and neutralization by murine monoclonal and human polyclonal antibodies. All mutants made capsid proteins within a level about 20-fold of that made by the wild type. All but seven mutants bound heparin as well as the wild type. Forty-two mutants transduced human cells at least as well as the wild type, and 10 mutants increased transducing activity up to ninefold more than the wild type. Eighteen adjacent alanine substitutions diminished transduction from 10- to 100,000-fold but had no effect on heparin binding and define an area (dead zone) required for transduction that is distinct from the previously characterized heparin receptor binding site. Mutations that reduced binding and neutralization by a murine monoclonal antibody (A20) were localized, while mutations that reduced neutralization by individual human sera or by pooled human, intravenous immunoglobulin G (IVIG) were dispersed over a larger area. Mutations that reduced binding by A20 also reduced neutralization. However, a mutation that reduced the binding of IVIG by 90% did not reduce neutralization, and mutations that reduced neutralization by IVIG did not reduce its binding. Combinations of mutations did not significantly increase transduction or resistance to neutralization by IVIG. These mutations define areas on the surface of the AAV-2 capsid that are important determinants of transduction and antibody neutralization.

Indexed as

Neutralization TestsTransduction, GeneticAlanineAmino Acid SubstitutionAnimalsAntibodies, MonoclonalAntibodies, ViralCapsidDependovirusHeparinHumansImmune SeraMiceModels, MolecularMutationAlanineAntibodies, MonoclonalAntibodies, ViralHeparinImmune Sera

Identifiers

PMID16378984
PMCPMC1346838
OpenAlexW2105176806

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.