ArticleCell2020
Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies.
Open access · bronzeAbstract read
In one paragraph
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 2 pooled it
11.1field-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
132 citing papers in PubMed, 2 syntheses or guidelines pooled it, 185 citations in OpenAlex.
- Virus-directed CAR immunotherapies for chronic HBV and HIV: a systematic synthesis of preclinical and early clinical evidences.Frontiers in medicine · 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
- Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.Stem cell research & therapy · 2026Review
- Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- CAR-T cells in solid tumors: engineering, biomarkers, translational pathways and the road ahead.Frontiers in immunology · 2026Review
- Beyond synthetic lethality in large-scale metabolic and regulatory network models via genetic minimal intervention set.Bioinformatics advances · 2026Article
- SEED-Selection enables high-efficiency enrichment of primary T cells edited at multiple loci.Nature biotechnology · 2025Article
- A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025Article
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- CAR-engineered lymphocyte persistence is governed by a FAS ligand-FAS autoregulatory circuit.Nature cancer · 2025Article
- CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.Trends in cancer · 2025Review
- Requirement for Cyclin D1 Underlies Cell-Autonomous HIF2 Dependence in Kidney Cancer.Cancer discovery · 2025Article
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- Engineering CAR-T Therapeutics for Enhanced Solid Tumor Targeting.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Engineering tripartite gene editing machinery for highly efficient non-viral targeted genome integration.Nature communications · 2025Article
- Bioprinted platform for parallelized screening of engineered microtissues in vivo.Cell stem cell · 2025Article
- HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy.Cell · 2025Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Theodore L RothMedical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. Electronic address: theodore.roth@ucsf.edu.
P Jonathan LiDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Franziska BlaeschkeDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Jasper F NiesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Ryan ApathyDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Cody MoweryMedical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Ruby YuDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Michelle L T NguyenDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Youjin LeeDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Anna TruongDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Joseph HiattMedical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
David WuMedical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
David N NguyenDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Daniel GoodmanDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Jeffrey A BluestoneDiabetes Center, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Sean N. Parker Autoimmune Research Laboratory, University of California, San Francisco, San Francisco, CA, USA.
Chun Jimmie YeParker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Institute of Computational Health Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Kole RoybalDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA; Sean N. Parker Autoimmune Research Laboratory, University of California, San Francisco, San Francisco, CA, USA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Eric ShifrutDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Alexander MarsonDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: alexander.marson@ucsf.edu.
University of California, San Francisco · 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 VAISSE, CHRISTIAN · 2003 to 2019
$21.8MX-ray Screening and Rapid Structure DeterminationP50AI150476 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2019 to 2021
$14.4MDIABETES, 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
$11.0MRESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2MFunctional Interrogation of Non-Coding Type 1 Diabetes Risk Variants in Human Immune Cells and Beta CellsDP3DK111914 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSON, ALEXANDER · 2016 to 2016
$3.7MFunctional Testing of Host Genes that Control HIV Latency in Primary Immune CellsDP2DA042423 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSON, ALEXANDER · 2016 to 2016
$2.4MFunctional Molecular Investigation of Inflammatory Bowel Disease (IBD) Risk VariantsR01DK119979 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSON, ALEXANDER · 2018 to 2021
$671kBD FACSAria Fusion Cell SorterS10OD021822 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEE, MICHAEL R. · 2016 to 2016
$573kEndogenous T Cell Receptor Replacement in Autoimmune DiabetesF30DK120213 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROTH, THEODORE LEE · 2018 to 2020
$64kNIAID NIH HHS L30 AI113413NIAID NIH HHS L40 AI140341NIAID NIH HHS P50 AI150476NIAID NIH HHS T32 AI007334NIAMS NIH HHS P30 AR070155NIDA NIH HHS DP2 DA042423NIDDK NIH HHS DP3 DK111914NIDDK NIH HHS F30 DK120213NIDDK NIH HHS P30 DK063720NIDDK NIH HHS R01 DK119979NIDDK NIH HHS T32 DK007418NIGMS NIH HHS T32 GM007618NIH HHS S10 OD021822
Abstract
Adoptive transfer of genetically modified immune cells holds great promise for cancer immunotherapy. CRISPR knockin targeting can improve cell therapies, but more high-throughput methods are needed to test which knockin gene constructs most potently enhance primary cell functions in vivo. We developed a widely adaptable technology to barcode and track targeted integrations of large non-viral DNA templates and applied it to perform pooled knockin screens in primary human T cells. Pooled knockin of dozens of unique barcoded templates into the T cell receptor (TCR)-locus revealed gene constructs that enhanced fitness in vitro and in vivo. We further developed pooled knockin sequencing (PoKI-seq), combining single-cell transcriptome analysis and pooled knockin screening to measure cell abundance and cell state ex vivo and in vivo. This platform nominated a novel transforming growth factor β (TGF-β) R2-41BB chimeric receptor that improved solid tumor clearance. Pooled knockin screening enables parallelized re-writing of endogenous genetic sequences to accelerate discovery of knockin programs for cell therapies.
Indexed as
AnimalsBlood CellsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGene Knock-In TechniquesGenetic EngineeringHumansImmunotherapyMiceMice, Inbred NODMice, SCIDRNA, Guide, CRISPR-Cas SystemsSingle-Cell AnalysisT-LymphocytesTranscriptomeRNA, Guide, CRISPR-Cas Systemscell therapyCRISPRhuman T cellknockinspooled screensingle-cell RNA-seq
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