ArticleCell2023
Modular pooled discovery of synthetic knockin sequences to program durable cell therapies.
Open access · bronzeAbstract read
In one paragraph
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 2 pooled it
13.6field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Allogeneic CAR-engineered cellular therapy for relapsed and refractory large B cell lymphoma: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- CRISPRing through time: How cutting-edge technology is revolutionizing life sciences and medicine.Molecular therapy. Nucleic acids · 2026Review
- Article
- Surfaceome CRISPR activation screening uncovers ligands regulating tumor sensitivity to NK cell killing.Nature communications · 2026Article
- Tumor irradiation promotes antigen dressing of dendritic cells to enhance CAR T cell persistence and efficacy in lung metastases.Nature cancer · 2026Article
- Single-cell gain-of-function mapping reveals latent regulatory programs governing CD8Research square · 2026Article
- A combinatorial domain screening platform reveals epigenetic effector interactions for transcriptional perturbation.Nature communications · 2026Article
- Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026Article
- Fine-tuning BACH2 dosage balances stemness and effector function to enhance antitumor T cell therapy.Nature immunology · 2026Article
- Article
- CAR-macrophages: a new chapter in cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Article
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- Latent Regulatory Programs Generate Synthetic T Cell States with Enhanced Therapeutic Potential.bioRxiv : the preprint server for biology · 2026Article
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- SEED-Selection enables high-efficiency enrichment of primary T cells edited at multiple loci.Nature biotechnology · 2025Article
- Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.Inflammation and regeneration · 2025Review
- A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025Article
- Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency.Cancer cell · 2025Article
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 4 institutions in 2 countries.
Franziska BlaeschkeGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Yan Yi ChenGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Ryan ApathyGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Bence DanielGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Andy Y ChenGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Peixin Amy ChenGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Katalin SandorGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Wenxi ZhangGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Zhongmei LiGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Cody T MoweryGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Tori N YamamotoGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
William A NybergGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Angela ToGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Ruby YuGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Raymund BuenoInstitute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA.
Min Cheol KimInstitute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA.
Ralf SchmidtGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Daniel B GoodmanGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94129, USA.
Tobias FeuchtingerDepartment of Pediatric Hematology, Oncology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich 80337, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich 80336, Germany; National Center for Infection Research (DZIF), Munich 81377, Germany.
Justin EyquemGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94129, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Chun Jimmie YeGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94129, USA; Institute for Computational Health Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Julia CarnevaleGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94129, USA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Ansuman T SatpathyGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94129, USA; Program in Immunology, Stanford University, Stanford, CA 94305, USA.
Eric ShifrutGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Theodore L RothDepartment of Pathology, Stanford University, Stanford, CA 94305, USA. Electronic address: troth@stanford.edu.
Alexander MarsonGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94129, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Innovative Genomics Institute, University of California Berkeley, Berkeley, CA 94720, USA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: alexander.marson@ucsf.edu.
Gladstone Institutes · USUniversity of California, San Francisco · USGerman Center for Infection Research · DEStanford Medicine · US
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6MResearch BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8MDIABETES, ENDOCRINOLOGY &METABOLISM TRAINING PROGRAMT32DK007418 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARD C HSIAO · 1986 to 2026
$14.3MMOLECULAR AND CELLULAR IMMUNOLOGYT32AI007334 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1988 to 2023
$11.0MMolecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4MRestorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5MMapping gene-by-environment interactions using multiplexed single cell RNA-sequencingR01HG011239 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2020 to 2023
$4.1MGenetic regulation and immunological function of ERAP2 haplotypesR01AI136972 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2018 to 2022
$3.5MDecoding and reprogramming T cells through synthetic biology for cancer immunotherapyR01CA276368 · NCI · J. DAVID GLADSTONE INSTITUTES · PI Alexander Marson, Kole T Roybal · 2023 to 2026
$3.0MTargeting 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
$1.3MDissecting intrinsic variability in engineered T Cell immunotherapiesK08CA286740 · NCI · STANFORD UNIVERSITY · PI Theodore Lee Roth · 2024 to 2026
$747kIllumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583kNCI NIH HHS K08 CA252605NCI NIH HHS K08 CA286740NCI NIH HHS R01 CA276368NCI NIH HHS T32 CA108462NCRR NIH HHS S10 RR028962NHGRI NIH HHS R01 HG011239NIAID NIH HHS R01 AI136972NIAID NIH HHS T32 AI007334NIDDK NIH HHS F30 DK120213NIDDK NIH HHS P30 DK063720NIDDK NIH HHS T32 DK007418NIGMS NIH HHS T32 GM007618NIGMS NIH HHS T32 GM136547NIH HHS S10 OD021822NIH HHS S10 OD028511
Abstract
Chronic stimulation can cause T cell dysfunction and limit the efficacy of cellular immunotherapies. Improved methods are required to compare large numbers of synthetic knockin (KI) sequences to reprogram cell functions. Here, we developed modular pooled KI screening (ModPoKI), an adaptable platform for modular construction of DNA KI libraries using barcoded multicistronic adaptors. We built two ModPoKI libraries of 100 transcription factors (TFs) and 129 natural and synthetic surface receptors (SRs). Over 30 ModPoKI screens across human TCR- and CAR-T cells in diverse conditions identified a transcription factor AP4 (TFAP4) construct that enhanced fitness of chronically stimulated CAR-T cells and anti-cancer function in vitro and in vivo. ModPoKI's modularity allowed us to generate an ∼10,000-member library of TF combinations. Non-viral KI of a combined BATF-TFAP4 polycistronic construct enhanced fitness. Overexpressed BATF and TFAP4 co-occupy and regulate key gene targets to reprogram T cell function. ModPoKI facilitates the discovery of complex gene constructs to program cellular functions.
Indexed as
Cell- and Tissue-Based TherapyExerciseGene LibraryHumansImmunotherapyResearchchimeric antigen receptorchronic stimulationCRISPRhuman T cellsimmunotherapyknockinspooled screenssynthetic surface receptortranscription factor
Identifiers
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.