Evidence map›Paper›PMID 36635967›Full record

ReviewMolecular therapy : the journal of the American Society of Gene Therapy2023

Binding and neutralizing anti-AAV antibodies: Detection and implications for rAAV-mediated gene therapy.

Martin Schulz, Daniel I Levy, Christos J Petropoulos, George Bashirians, Ian Winburn, Matthias Mahn, Suryanarayan Somanathan, Seng H Cheng, Barry J Byrne

Open access · hybridFull text readReview
In one paragraph

Review in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 2 pooled it
31.6field-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

89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.

  1. Pooled it
  2. A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Pooled it
  3. Review
  4. Article
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  9. SORT LNPs encapsulating Cas9 mRNA achieve efficient editing in skeletal muscle in a dystrophic mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Immune Toxicities in AAV Gene Therapy: Overview for Clinicians.International journal of molecular sciences · 2026
    Review

29 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

9 authors at 2 institutions in 1 country.

Martin SchulzPfizer, 235 East 42nd Street, New York, NY 10017, USA.
Daniel I LevyPfizer, 235 East 42nd Street, New York, NY 10017, USA.
Christos J PetropoulosLabcorp-Monogram Biosciences, South San Francisco, CA 94080, USA.
George BashiriansPfizer, 235 East 42nd Street, New York, NY 10017, USA.
Ian WinburnPfizer, 235 East 42nd Street, New York, NY 10017, USA.
Matthias MahnPfizer, 235 East 42nd Street, New York, NY 10017, USA.
Suryanarayan SomanathanPfizer, 235 East 42nd Street, New York, NY 10017, USA. Electronic address: suryanarayan.somanathan@pfizer.com.
Seng H ChengPfizer, 235 East 42nd Street, New York, NY 10017, USA.
Barry J ByrneUniversity of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA. Electronic address: barry.byrne@ufl.edu.
Pfizer (United States) · USUniversity of Florida · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Assessment of anti-adeno-associated virus (AAV) antibodies in patients prior to systemic gene therapy administration is an important consideration regarding efficacy and safety of the therapy. Approximately 30%-60% of individuals have pre-existing anti-AAV antibodies. Seroprevalence is impacted by multiple factors, including geography, age, capsid serotype, and assay type. Anti-AAV antibody assays typically measure (1) transduction inhibition by detecting the neutralizing capacity of antibodies and non-antibody neutralizing factors, or (2) total anti-capsid binding antibodies, regardless of neutralizing activity. Presently, there is a paucity of head-to-head data and standardized approaches associating assay results with clinical outcomes. In addition, establishing clinically relevant screening titer cutoffs is complex. Thus, meaningful comparisons across assays are nearly impossible. Although complex, establishing screening assays in routine clinical practice to identify patients with antibody levels that may impact favorable treatment outcomes is achievable for both transduction inhibition and total antibody assays. Formal regulatory approval of such assays as companion diagnostic tests will confirm their suitability for specific recombinant AAV gene therapies. This review covers current approaches to measure anti-AAV antibodies in patient plasma or serum, their potential impact on therapeutic safety and efficacy, and investigative strategies to mitigate the effects of pre-existing anti-AAV antibodies in patients.

Indexed as

Antibodies, NeutralizingDependovirusAntibodies, ViralCapsid ProteinsGenetic TherapyGenetic VectorsHumansSeroepidemiologic StudiesAntibodies, NeutralizingAntibodies, ViralCapsid Proteinsefficacygene therapyhumoral immunityneutralizing antibodiesrecombinant adeno-associated virussafetyseroprevalencetotal antibody assaytransduction inhibition assay

Identifiers

PMID36635967
PMCPMC10014285
OpenAlexW4315643308

What OpenQuestion holds

Textfull text, public
LicenceCC BY
reference markers read6
measurements read14
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.