Evidence map›Paper›PMID 33258500›Full record

ArticleThe EMBO journal2021

Multiplexed CRISPR/CAS9-mediated engineering of pre-clinical mouse models bearing native human B cell receptors.

Xuesong Wang, Rashmi Ray, Sven Kratochvil, Eleonora Melzi, Ying-Cing Lin, Sophie Giguere, Liling Xu, John Warner, Diane Cheon, Alessia Liguori and 10 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

40 citing papers in PubMed, 50 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Dynamic control of autoreactive B cells from spontaneous germinal centers.Journal of immunology (Baltimore, Md. : 1950) · 2025
    Article
  10. Antibody feedback establishes an affinity brake in the germinal center.bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Structural insights into VRC01-class bnAb precursors with diverse light chains elicited in the IAVI G001 human vaccine trial.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
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

20 authors at 3 institutions in 1 country.

Xuesong WangThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Rashmi RayThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Sven KratochvilThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Eleonora MelziThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.ORCID 0000-0002-1520-735X
Ying-Cing LinThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Sophie GiguereThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Liling XuThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
John WarnerThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Diane CheonThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Alessia LiguoriDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Bettina GroschelDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Nicole PhelpsDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Yumiko AdachiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Ryan TingleDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Lin WuGenome Modification Facility, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Shane CrottyConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
Kathrin H KirschThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.ORCID 0000-0003-1532-1715
Usha NairThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.ORCID 0000-0002-1927-6889
William R SchiefThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.ORCID 0000-0002-1120-0150
Facundo D BatistaThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.ORCID 0000-0002-1130-9463
Ragon Institute of MGH, MIT and Harvard · USScripps Research Institute · USHarvard University · US

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Gates Foundation OPP1214085HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) Al100663NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

B-cell receptor (BCR) knock-in (KI) mouse models play an important role in vaccine development and fundamental immunological studies. However, the time required to generate them poses a bottleneck. Here we report a one-step CRISPR/Cas9 KI methodology to combine the insertion of human germline immunoglobulin heavy and light chains at their endogenous loci in mice. We validate this technology with the rapid generation of three BCR KI lines expressing native human precursors, instead of computationally inferred germline sequences, to HIV broadly neutralizing antibodies. We demonstrate that B cells from these mice are fully functional: upon transfer to congenic, wild type mice at controlled frequencies, such B cells can be primed by eOD-GT8 60mer, a germline-targeting immunogen currently in clinical trials, recruited to germinal centers, secrete class-switched antibodies, undergo somatic hypermutation, and differentiate into memory B cells. KI mice expressing functional human BCRs promise to accelerate the development of vaccines for HIV and other infectious diseases.

Indexed as

AnimalsB-LymphocytesBroadly Neutralizing AntibodiesCell LineCRISPR-Cas SystemsGene Knock-In TechniquesGerminal CenterHEK293 CellsHIV-1HumansMaleMiceMice, Inbred C57BLModels, AnimalReceptors, Antigen, B-CellBroadly Neutralizing AntibodiesReceptors, Antigen, B-CellantibodyB cell receptorCas9CRISPRHIV vaccineknock-in

Identifiers

PMID33258500
PMCPMC7809789
OpenAlexW3108160938

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.