ArticleNature biotechnology2023
Massively parallel knock-in engineering of human T cells.
Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed.
- CRISPR-Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus.Molecular biology reports · 2026Review
- Metabolic profiling of CAR T-cells in patients reveals a shift toward amino acid-supported OXPHOS and informs transporter engineering.Research square · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Next-generation CAR-T engineering for colorectal cancer: integrating targets, tumor microenvironment barriers, and emerging strategies.Frontiers in immunology · 2026Review
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- Beyond synthetic lethality in large-scale metabolic and regulatory network models via genetic minimal intervention set.Bioinformatics advances · 2026Article
- Convergence of mRNA technology and chimeric antigen receptor therapy: targeted technology optimizing targeted therapy.Journal of translational medicine · 2025Review
- 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
- Efficient and multiplexed somatic genome editing with Cas12a mice.Nature biomedical engineering · 2025Article
- Article
- Synergically enhanced anti-tumor immunity of in vivo panCAR by circRNA vaccine boosting.Cell reports. Medicine · 2025Article
- Engineering resilient CAR T cells for immunosuppressive environment.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Post-cleavage target residence determines asymmetry in non-homologous end joining of Cas12a-induced DNA double strand breaks.Genome biology · 2025Article
- Mapping variant effects on anti-tumor hallmarks of primary human T cells with base-editing screens.Nature biotechnology · 2025Article
- Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies.Oncogene · 2025Review
- Genetic disruption of Blimp-1 drastically augments the antitumor efficacy of BCMA-targeting CAR T cells.Blood advances · 2025Article
- Unraveling the future of genomics: CRISPR, single-cell omics, and the applications in cancer and immunology.Frontiers in genome editing · 2025Review
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15 authors.
Funding
Abstract
The efficiency of targeted knock-in for cell therapeutic applications is generally low, and the scale is limited. In this study, we developed CLASH, a system that enables high-efficiency, high-throughput knock-in engineering. In CLASH, Cas12a/Cpf1 mRNA combined with pooled adeno-associated viruses mediate simultaneous gene editing and precise transgene knock-in using massively parallel homology-directed repair, thereby producing a pool of stably integrated mutant variants each with targeted gene editing. We applied this technology in primary human T cells and performed time-coursed CLASH experiments in blood cancer and solid tumor models using CD3, CD8 and CD4 T cells, enabling pooled generation and unbiased selection of favorable CAR-T variants. Emerging from CLASH experiments, a unique CRISPR RNA (crRNA) generates an exon3 skip mutant of PRDM1 in CAR-Ts, which leads to increased proliferation, stem-like properties, central memory and longevity in these cells, resulting in higher efficacy in vivo across multiple cancer models, including a solid tumor model. The versatility of CLASH makes it broadly applicable to diverse cellular and therapeutic engineering applications.
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Registered trials
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.