Evidence map›Paper›PMID 41120666›Full record

ArticleNature biotechnology2026

Integrated epigenetic and genetic programming of primary human T cells.

Laine Goudy, Alvin Ha, Ashir A Borah, Jennifer M Umhoefer, Lauren Chow, Carinna Tran, Aidan Winters, Alexis Talbot, Rosmely Hernandez, Zhongmei Li and 13 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
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

19 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025
    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

23 authors.

Laine GoudyGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Alvin HaGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7092-9072
Ashir A BorahArc Institute, Palo Alto, CA, USA.
Jennifer M UmhoeferGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Lauren ChowGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Carinna TranGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Aidan WintersArc Institute, Palo Alto, CA, USA.
Alexis TalbotDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6734-413X
Rosmely HernandezGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Zhongmei LiGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Sanjana SubramanyaGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2503-7200
Abolfazl ArabArc Institute, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-0024-2937
Nupura KaleDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3185-8646
Jae Hyun J LeeGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.ORCID http://orcid.org/0009-0009-2998-5249
Joseph J MuldoonGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3784-3565
Chang LiuGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Ralf SchmidtGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Philip SantangeloPetit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-7352-0339
Julia CarnevaleGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9410-7148
Justin EyquemGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA. justin.eyquem@ucsf.edu.ORCID http://orcid.org/0000-0001-8262-1190
Brian R ShyGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA. brian.shy@ucsf.edu.ORCID http://orcid.org/0000-0001-9569-3708
Alex MarsonGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA. alex.marson@gladstone.ucsf.edu.ORCID http://orcid.org/0000-0002-2734-5776
Luke A GilbertArc Institute, Palo Alto, CA, USA. luke@arcinstitute.org.ORCID http://orcid.org/0000-0001-5854-0825

Funding

Spatial multiomic mapping of gene function with CRISPRoffUM1HG012660 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Luke Gilbert · 2022 to 2026
$8.2M
A GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4M
Targeting SOCS1 and RASA2 to Engineer More Potent Adoptive T Cell Therapies for Cancer Treatment.K08CA252605 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CARNEVALE, JULIA C · 2020 to 2024
$1.3M
Non-viral genome, epigenome, and transcriptome engineering for clinical CAR-T cell manufacturingK08CA273529 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian R Shy · 2022 to 2026
$1.2M
National Science Foundation (NSF) 2021316455)NCATS NIH HHS L30 TR002983NCI NIH HHS DP2 CA239597NCI NIH HHS K08 CA252605NCI NIH HHS K08 CA273529NHGRI NIH HHS UM1 HG012660U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1K08CA252605-01U.S. Department of Health & Human Services | National Institutes of Health (NIH) K08CA273529U.S. Department of Health & Human Services | National Institutes of Health (NIH) L30TR002983U.S. Department of Health & Human Services | National Institutes of Health (NIH) UM1HG012660
6 · The paper itself

Abstract

Targeted epigenetic engineering of gene expression in cell therapies would allow programming of desirable phenotypes without many of the challenges and safety risks associated with double-strand break-based genetic editing approaches. Here, we develop an all-RNA platform for efficient, durable and multiplexed epigenetic programming in primary human T cells, stably turning endogenous genes off or on using CRISPRoff and CRISPRon epigenetic editors. We achieve epigenetic programming of diverse targeted genomic elements without the need for sustained expression of CRISPR systems. CRISPRoff-mediated gene silencing is maintained through numerous cell divisions, T cell stimulations and in vivo adoptive transfer, avoiding cytotoxicity or chromosomal abnormalities inherent to multiplexed Cas9-mediated genome editing. Lastly, we successfully combined genetic and epigenetic engineering using orthogonal CRISPR Cas12a-dCas9 systems for targeted chimeric antigen receptor (CAR) knock-in and CRISPRoff silencing of therapeutically relevant genes to improve preclinical CAR-T cell-mediated in vivo tumor control and survival.

Indexed as

Epigenesis, GeneticGene EditingT-LymphocytesAnimalsCRISPR-Cas SystemsEpigenome EditingHumansReceptors, Chimeric AntigenReceptors, Chimeric Antigen

Identifiers

PMID41120666
PMCPMC13336058

What OpenQuestion 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 OpenQuestion graph.