Evidence map›Paper›PMID 38486104›Full record

ArticleNature biomedical engineering2024

In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies.

Yiming Yin, Yan Guo, Yuxuan Jiang, Brian Quinlan, Haiyong Peng, Gogce Crynen, Wenhui He, Lizhou Zhang, Tianling Ou, Charles C Bailey and 1 more

Open access · greenAbstract read
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
6.9field-weighted citation impact, top 3% 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

17 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Toward CAR-B cells for HIV-1 therapy.Molecular therapy. Methods & clinical development · 2025
    Article
  8. Review
  9. Article
  10. Review
  11. CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Research square · 2024
    Article
4 · The record

Corrections and comments

  • Update of
    2023
5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Yiming YinDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. yiming.yin@childrens.harvard.edu.ORCID http://orcid.org/0000-0003-0087-2784
Yan GuoDepartment of Immunology and Microbiology, Scripps Biomedical Research, University of Florida, Jupiter, FL, USA.
Yuxuan JiangInstitute of Biomechanics and Medical Engineering, AML, Department of Engineering Mechanics, Tsinghua University, Beijing, People's Republic of China.
Brian QuinlanDepartment of Immunology and Microbiology, Scripps Biomedical Research, University of Florida, Jupiter, FL, USA.
Haiyong PengDepartment of Immunology and Microbiology, Scripps Biomedical Research, University of Florida, Jupiter, FL, USA.ORCID http://orcid.org/0000-0003-0312-1337
Gogce CrynenDepartment of Immunology and Microbiology, Scripps Biomedical Research, University of Florida, Jupiter, FL, USA.
Wenhui HeDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Lizhou ZhangDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Tianling OuDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5119-2239
Charles C BaileyThe Center for Integrated Solutions to Infectious Diseases (CISID), The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael FarzanDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2990-5319
Broad Institute · USScripps Research Institute · USBoston Children's Hospital · USTsinghua University · CN

Funding

Project 4: A permanent off-switch for AAVU19AI149646 · NIAID · UNIVERSITY OF FLORIDA · PI DESROSIERS, RONALD C · 2020 to 2024
$14.0M
Engineering CAR-B cells for an HIV-1 functional cureR01DA056771 · NIDA · UNIVERSITY OF FLORIDA · PI Michael R. Farzan · 2022 to 2026
$3.5M
In vivo transformation of chimeric antigen receptor B cells for a functional cure of HIVR01AI174277 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Hyeryun Choe, Michael R. Farzan · 2023 to 2026
$3.3M
Safe, CRISPR/Cas-free B cell editing for therapeutic applicationsR21AI178031 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI FARZAN, MICHAEL R. · 2023 to 2024
$487k
NIAID NIH HHS R01 AI174277NIAID NIH HHS R21 AI178031NIAID NIH HHS U19 AI149646NIDA NIH HHS R01 DA056771
6 · The paper itself

Abstract

Mice adoptively transferred with mouse B cells edited via CRISPR to express human antibody variable chains could help evaluate candidate vaccines and develop better antibody therapies. However, current editing strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that these key B-cell functions can be preserved by directly and simultaneously replacing recombined mouse heavy and kappa chains with those of human antibodies, using a single Cas12a-mediated cut at each locus and 5' homology arms complementary to distal V segments. Cells edited in this way to express the human immunodeficiency virus type 1 (HIV-1) broadly neutralizing antibody 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated mice. The 10-1074 variants isolated from the mice neutralized a global panel of HIV-1 isolates more efficiently than wild-type 10-1074 while maintaining its low polyreactivity and long half-life. We also used the approach to improve the potency of anti-SARS-CoV-2 antibodies against recent Omicron strains. In vivo affinity maturation of B cells edited at their native loci may facilitate the development of broad, potent and bioavailable antibodies.

Indexed as

Antibodies, NeutralizingB-LymphocytesCOVID-19HIV-1HIV AntibodiesSARS-CoV-2AnimalsAntibodies, ViralAntibody AffinityCOVID-19 VaccinesCRISPR-Cas SystemsHumansMiceMice, Inbred C57BLAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesHIV Antibodies

Identifiers

PMID38486104
PMCPMC12090756
OpenAlexW4392809342

What OpenQuestion holds

Textmetadata
LicenceTDM
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.