Evidence map›Paper›PMID 37436182›Full record

ArticleAnalytical chemistry2023

Antibody Binding to Recombinant Adeno Associated Virus Monitored by Charge Detection Mass Spectrometry.

Ashley E Grande, Xin Li, Lohra M Miller, Junping Zhang, Benjamin E Draper, Roland W Herzog, Weidong Xiao, Martin F Jarrold

Open access · greenAbstract read
In one paragraph

Article in Analytical chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
5.0field-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

10 citing papers in PubMed, 16 citations in OpenAlex.

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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 2 institutions in 1 country.

Ashley E GrandeChemistry Department, Indiana University, 800 E Kirkwood Ave, Bloomington, Indiana 47405, United States.
Xin LiHerman B. Wells Center for Pediatric Research, Indiana University, Indianapolis, Indiana 46202, United States.
Lohra M MillerChemistry Department, Indiana University, 800 E Kirkwood Ave, Bloomington, Indiana 47405, United States.
Junping ZhangHerman B. Wells Center for Pediatric Research, Indiana University, Indianapolis, Indiana 46202, United States.
Benjamin E DraperMegadalton Solutions Inc., 3750 E Bluebird Ln, Bloomington, Indiana 47401, United States.
Roland W HerzogHerman B. Wells Center for Pediatric Research, Indiana University, Indianapolis, Indiana 46202, United States.
Weidong XiaoHerman B. Wells Center for Pediatric Research, Indiana University, Indianapolis, Indiana 46202, United States.
Martin F JarroldChemistry Department, Indiana University, 800 E Kirkwood Ave, Bloomington, Indiana 47405, United States.ORCID 0000-0001-7084-176X
Indiana University – Purdue University Indianapolis · USIndiana University Bloomington · US

Funding

Toward Safer Gene Therapy for Hemophilia AP01HL160472 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI Roland W. Herzog · 2022 to 2026
$15.1M
Temple Project 1: Genetic characterization of factor VIII Inhibitors and glydosylation patternsU54HL142019 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI LI, LEI, MIAO, CAROL H · 2018 to 2022
$6.9M
Novel adeno-associated virus vector production system developmentR01HL114152 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI XIAO, WEIDONG · 2012 to 2016
$2.2M
NHLBI NIH HHS P01 HL160472NHLBI NIH HHS R01 HL114152NHLBI NIH HHS U54 HL142019
6 · The paper itself

Abstract

Recombinant adeno-associated virus (rAAV) is a leading gene therapy vector. However, neutralizing antibodies reduce its efficacy. Traditional methods used to investigate antibody binding provide limited information. Here, charge detection mass spectrometry (CD-MS) was used to investigate the binding of monoclonal antibody ADK8 to AAV serotype 8 (AAV8). CD-MS provides a label-free approach to antibody binding. Individual binding events can be monitored as each event is indicated by a shift of the antibody-antigen complex to a higher mass. Unlike other methods, the CD-MS approach reveals the distribution of antibodies bound on capsids, allowing AAV8 subpopulations with different affinities to be identified. The charge state generated by the electrospray of large ions is normally correlated with the structure, and the charge is expected to increase when an antibody binds to the capsid exterior. Surprisingly, binding of the first ADK8 to AAV8 causes a substantial decrease in the charge, suggesting that the first antibody binding event causes a significant structural change. The charge increases for subsequent binding events. Finally, high ADK8 concentrations cause agglutination, where ADK8 links AAV capsids to form dimers and higher order multimers.

Indexed as

Antibodies, NeutralizingDependovirusCapsidCapsid ProteinsGenetic VectorsAntibodies, NeutralizingCapsid Proteins

Identifiers

PMID37436182
PMCPMC12048215
OpenAlexW4383999236

What OpenQuestion holds

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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.