Evidence map›Paper›PMID 30648968›Full record

ArticleeLife2019

Reprogramming the antigen specificity of B cells using genome-editing technologies.

James E Voss, Alicia Gonzalez-Martin, Raiees Andrabi, Roberta P Fuller, Ben Murrell, Laura E McCoy, Katelyn Porter, Deli Huang, Wenjuan Li, Devin Sok and 9 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
4.5field-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

62 citing papers in PubMed, 95 citations in OpenAlex.

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  12. Biomaterial-Based Therapeutic Delivery of Immune Cells.Advanced healthcare materials · 2025
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  16. Blunting specific T-dependent antibody responses with engineered "decoy" B cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  17. Human plasma cells engineered to secrete bispecifics drive effective in vivo leukemia killing.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  18. Review
  19. Article
  20. Article

2 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

19 authors at 5 institutions in 4 countries.

James E Voss *Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.ORCID 0000-0002-4777-1596
Alicia Gonzalez-Martin *Department of Biochemistry, Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain.
Raiees Andrabi *Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Roberta P Fuller *Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Ben Murrell *Department of Medicine, University of California, San Diego, San Diego, United States.
Laura E McCoy *Division of Infection and Immunity, University College London, London, United Kingdom.
Katelyn Porter *Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Deli HuangDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Wenjuan LiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Devin SokDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Khoa LeDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Bryan BrineyDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Morgan ChateauDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, United States.
Geoffrey RogersDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, United States.
Lars HangartnerDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Ann J FeeneyDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
David NemazeeDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Paula CannonDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, United States.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States.
Scripps Research Institute · USUniversity of Southern California · USInstituto de Investigaciones Biomédicas Sols-Morreale · ESKarolinska Institutet · SEUniversity College London · GB

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Scripps Translational Science InstituteUL1TR001114 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2013 to 2017
$24.0M
Knock-in mice expressing germline-reverted broadly neutralizing HIV antibodiesR01AI073148 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2007 to 2023
$8.2M
Genomic modification with purified nuclease proteins for HIV-1 therapyR01DE025167 · NIDCR · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2014 to 2018
$3.7M
Immune Tolerance in Non-Clonal Immune SystemsR37AI059714 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2014 to 2020
$3.5M
Bill and Melinda Gates Foundation OPP1183956FP7 People: Marie-Curie Actions FP7-PEOPLE-2013-IOFMarie-Curie Fellowship FP7-PEOPLE-2013-IOFMedical Research Council MR/R008698/1Ministerio de Ciencia, Innovacion y Universidades Ramón y Cajal Merit Award RYC-2016-21155NCATS NIH HHS UL1 TR001114NIAID NIH HHS R01 AI073148NIAID NIH HHS R37 AI059714NIAID NIH HHS UM1 AI100663NIDCR NIH HHS R01 DE025167NIH HHS 5R01DE025167-05Ramón y Cajal Merit Award, Ministerio de Ciencia, Innovacion y Universidades RYC-2016-21155
6 · The paper itself

Abstract

We have developed a method to introduce novel paratopes into the human antibody repertoire by modifying the immunoglobulin (Ig) genes of mature B cells directly using genome editing technologies. We used CRISPR-Cas9 in a homology directed repair strategy, to replace the heavy chain (HC) variable region in B cell lines with that from an HIV broadly neutralizing antibody (bnAb), PG9. Our strategy is designed to function in cells that have undergone VDJ recombination using any combination of variable (V), diversity (D) and joining (J) genes. The modified locus expresses PG9 HC which pairs with native light chains (LCs) resulting in the cell surface expression of HIV specific B cell receptors (BCRs). Endogenous activation-induced cytidine deaminase (AID) in engineered cells allowed for Ig class switching and generated BCR variants with improved HIV neutralizing activity. Thus, BCRs engineered in this way retain the genetic flexibility normally required for affinity maturation during adaptive immune responses. Peripheral blood derived primary B cells from three different donors were edited using this strategy. Engineered cells could bind the PG9 epitope and sequenced mRNA showed PG9 HC transcribed as several different isotypes after culture with CD40 ligand and IL-4.

Indexed as

AICDA (Activation-Induced Cytidine Deaminase)Antibodies, NeutralizingAntibody SpecificityAntigen-Antibody ReactionsB-LymphocytesCell LineCRISPR-Cas SystemsCytidine DeaminaseGene EditingHIV AntibodiesHumansImmunoglobulin Heavy ChainsReceptors, Antigen, B-CellAICDA (Activation-Induced Cytidine Deaminase)Antibodies, NeutralizingCytidine DeaminaseHIV AntibodiesImmunoglobulin Heavy ChainsReceptors, Antigen, B-CellB cellbnAbCAR-BengineeringHIVhumanimmunologyinfectious diseaseinflammationmicrobiologyvaccine

Identifiers

PMID30648968
PMCPMC6355199
OpenAlexW2898192919

What Socratic holds

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LicenceCC BY
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 Socratic graph.