Evidence map›Paper›PMID 35356756›Full record

ReviewMolecular therapy. Methods & clinical development2022

Testing preexisting antibodies prior to AAV gene transfer therapy: rationale, lessons and future considerations.

Jerry R Mendell, Anne M Connolly, Kelly J Lehman, Danielle A Griffin, Sohrab Z Khan, Sachi D Dharia, Lucía Quintana-Gallardo, Louise R Rodino-Klapac

Open access · goldAbstract readReview
In one paragraph

Review in Molecular therapy. Methods & clinical development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
17.8field-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

82 citing papers in PubMed, 108 citations in OpenAlex.

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  15. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
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22 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 1 country.

Jerry R MendellCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Anne M ConnollyCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Kelly J LehmanCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Danielle A GriffinSarepta Therapeutics, Inc., 215 First Street, Cambridge, MA 02142, USA.
Sohrab Z KhanSarepta Therapeutics, Inc., 215 First Street, Cambridge, MA 02142, USA.
Sachi D DhariaSarepta Therapeutics, Inc., 215 First Street, Cambridge, MA 02142, USA.
Lucía Quintana-GallardoSarepta Therapeutics, Inc., 215 First Street, Cambridge, MA 02142, USA.
Louise R Rodino-KlapacCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Sarepta Therapeutics (United States) · USNationwide Children's Hospital · USThe Ohio State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Given the increasing number of gene transfer therapy studies either completed or underway, there is growing attention to the importance of preexisting adaptive immunity to the viral vectors used. The recombinant viral vectors developed for gene transfer therapy share structural features with naturally occurring wild-type virus. Antibodies generated against viral vectors obtained through a previous exposure to wild-type virus can potentially compromise transgene expression by blocking transduction, thereby limiting the therapeutic efficacy of the gene transfer therapy; they may also pose potential safety concerns. Therefore, systemic gene transfer delivery requires testing patients for preexisting antibodies. Two different assays have been used: (1) binding assays that focus on total antibodies (both neutralizing and non-neutralizing) and (2) neutralizing assays that detect neutralizing antibodies. In this review we focus on adeno-associated virus-based gene therapies, describing the immune response that occurs to naturally occurring adeno-associated viruses, the implications for patients with this exposure, the assays used to detect preexisting immune responses, and strategies to circumvent preexisting adaptive immunity to expand the patient base that could benefit from such therapies.

Indexed as

adeno-associated virusantibodiesassaysbinding assaysefficacygene transfer therapyimmunityneutralizing assayssafetytiter

Identifiers

PMID35356756
PMCPMC8933338
OpenAlexW4214625899

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.