Evidence map›Paper›PMID 38012416›Full record

ArticleNature immunology2024

X-CHIME enables combinatorial, inducible, lineage-specific and sequential knockout of genes in the immune system.

Martin W LaFleur, Ashlyn M Lemmen, Ivy S L Streeter, Thao H Nguyen, Lauren E Milling, Nicole M Derosia, Zachary M Hoffman, Jacob E Gillis, Qin Tjokrosurjo, Samuel C Markson and 6 more

Open access · greenAbstract read
In one paragraph

Article in Nature immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. A STUB1-CHIC2 complex inhibits CD8Nature immunology · 2025
    Article
  5. Review
  6. Infection and immunity · 2025
    Article
  7. THE BIOLOGY BEHIND PD-1 CHECKPOINT BLOCKADE.Transactions of the American Clinical and Climatological Association · 2025
    Review
  8. Framework for in vivo T cell screens.The Journal of experimental medicine · 2024
    Article
  9. Review
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

16 authors at 4 institutions in 1 country.

Martin W LaFleurDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Ashlyn M LemmenDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Ivy S L StreeterDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0729-1042
Thao H NguyenDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Lauren E MillingDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nicole M DerosiaDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Zachary M HoffmanDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Jacob E GillisDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Qin TjokrosurjoDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Samuel C MarksonDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9053-9867
Amy Y HuangDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6646-6503
Praju V AnekalMicRoN Core, Harvard Medical School, Boston, MA, USA.
Paula Montero LlopisMicRoN Core, Harvard Medical School, Boston, MA, USA.
W Nicholas HainingArsenal Biosciences, South San Francisco, CA, USA.
John G DoenchBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3707-9889
Arlene H SharpeDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Arlene_Sharpe@hms.harvard.edu.ORCID http://orcid.org/0000-0002-9736-2109
Brigham and Women's Hospital · USBroad Institute · USHarvard University · USArsenal Biosciences (United States) · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Role of Negative Costimulation in Regulation of AutoimmunityP01AI039671 · NIAID · YALE UNIVERSITY · PI David A. Hafler · 1996 to 2026
$51.7M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BLAZAR, BRUCE R · 2003 to 2023
$42.5M
Synergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dario AA Vignali · 2015 to 2026
$30.8M
Project 2: Genes required for dendritic cell responses to pathogens and T cellsU19AI133524 · NIAID · HARVARD MEDICAL SCHOOL · PI SHARPE, ARLENE H. · 2017 to 2021
$12.3M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2018 to 2022
$10.8M
NCI NIH HHS P30 CA006516NCI NIH HHS U54 CA225088NIAID NIH HHS P01 AI039671NIAID NIH HHS P01 AI056299NIAID NIH HHS P01 AI108545NIAID NIH HHS U19 AI133524
6 · The paper itself

Abstract

Annotation of immunologic gene function in vivo typically requires the generation of knockout mice, which is time consuming and low throughput. We previously developed CHimeric IMmune Editing (CHIME), a CRISPR-Cas9 bone marrow delivery system for constitutive, ubiquitous deletion of single genes. Here we describe X-CHIME, four new CHIME-based systems for modular and rapid interrogation of gene function combinatorially (C-CHIME), inducibly (I-CHIME), lineage-specifically (L-CHIME) or sequentially (S-CHIME). We use C-CHIME and S-CHIME to assess the consequences of combined deletion of Ptpn1 and Ptpn2, an embryonic lethal gene pair, in adult mice. We find that constitutive deletion of both PTPN1 and PTPN2 leads to bone marrow hypoplasia and lethality, while inducible deletion after immune development leads to enteritis and lethality. These findings demonstrate that X-CHIME can be used for rapid mechanistic evaluation of genes in distinct in vivo contexts and that PTPN1 and PTPN2 have some functional redundancy important for viability in adult mice.

Indexed as

CRISPR-Cas SystemsProtein Tyrosine Phosphatase, Non-Receptor Type 2AnimalsGene EditingImmune SystemMiceMice, KnockoutProtein Tyrosine Phosphatase, Non-Receptor Type 2Ptpn2 protein, mouse

Identifiers

PMID38012416
PMCPMC10881062
OpenAlexW4389058384

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.