ArticleNature biomedical engineering2025
Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering.
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Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10citing papers in PubMed
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Who cites it
10 citing papers in PubMed.
- A high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo.Science advances · 2026Article
- Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026Review
- Structural mining and engineering of metagenome-derived Cas12a orthologs expands the CRISPR genome editing and multiplex diagnostics toolkit.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Comparative characterization of Cas12f orthologs reveals mechanistic features underlying enhanced genome editing efficiency.Nature structural & molecular biology · 2026Article
- Advancing immunity and disease resistance in chickens through genome editing.Journal of animal science and biotechnology · 2026Review
- CRISPR-mediated conditional mutagenesis ofbioRxiv : the preprint server for biology · 2026Article
- 2025 in review.Nature biomedical engineering · 2025Article
- Review
- SWITCHER, a CRISPR-inducible floxed wild-type Cre regulating CRISPR activity.Communications biology · 2025Article
- Expanding the CRISPR/Cas toolkit: applications in proteomics and theranostics.Frontiers in bioengineering and biotechnology · 2025Review
Corrections and comments
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Authors and funding
37 authors.
Kaiyuan Tang *Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Liqun Zhou *Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-3561-7495
Xiaolong TianDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Shao-Yu FangDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Erica VandenbulckeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Andrew DuDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5823-2328
Johanna ShenDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Hanbing CaoDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Jerry ZhouDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Krista ChenDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Hyunu R KimDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Zhicheng LuoDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Shan XinDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-4735-0935
Shawn H LinDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-6909-467X
Daniel ParkDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0009-0002-6862-6635
Luojia YangDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Yueqi ZhangDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Kazushi SuzukiDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Medha MajetyDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Xinyu LingDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Stanley Z LamDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Ryan D ChowDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Ping RenDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Bo TaoSystem Biology Institute, Yale University, West Haven, CT, USA.
Keyi LiCombined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT, USA.
Adan CodinaDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Xiaoyun DaiDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Xingbo ShangSystem Biology Institute, Yale University, West Haven, CT, USA.
Suxia BaiDepartment of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Timothy NottoliDepartment of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2218-5590
Andre LevchenkoSystem Biology Institute, Yale University, West Haven, CT, USA.ORCID http://orcid.org/0000-0001-6262-1222
Carmen J BoothDepartment of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Chen LiuDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Rong FanSystem Biology Institute, Yale University, West Haven, CT, USA.ORCID http://orcid.org/0000-0001-7805-8059
Matthew B DongDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA. mdong11@jh.edu.ORCID http://orcid.org/0000-0003-2553-5186
Xiaoyu ZhouDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA. xiaoyu.zhou@yale.edu.ORCID http://orcid.org/0000-0002-2304-4191
Sidi ChenDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA. sidi.chen@yale.edu.ORCID http://orcid.org/0000-0002-3819-5005
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9MSystems analysis of phenotypic switch in control of cancer invasionU54CA209992 · NCI · YALE UNIVERSITY · PI LEVCHENKO, ANDRE · 2016 to 2021
$10.1M(PQ4) Novel tools for in vivo study of genetic interactions in cancer progressionR01CA231112 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2022
$3.0MHigh-throughput in vivo genetics for immunotherapy target discoveryDP2CA238295 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2018
$2.5MNew approaches for single cell tagging, editing and profiling of glial cells in vivoRF1DA048811 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HONG, WEIZHE · 2019 to 2019
$2.4MAdvanced development of composite gene delivery and CAR engineering systemsR33CA281702 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2023 to 2025
$1.2MRapidly scalable platforms for direct in vivo screening of functional drivers in lethal cancersR33CA225498 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2019 to 2021
$1.2MReprogramming T cell function with multiplexed genome engineering to develop next-generation immunotherapyK99CA282989 · NCI · YALE UNIVERSITY · PI ZHOU, XIAOYU · 2024 to 2025
$285kMechanosensation in tumorigenesis and metastasisF30CA250249 · NCI · YALE UNIVERSITY · PI CHOW, RYAN D · 2020 to 2022
$113kNCI NIH HHS DP2 CA238295NCI NIH HHS F30 CA250249NCI NIH HHS K99 CA282989NCI NIH HHS R01 CA231112NCI NIH HHS R33 CA225498NCI NIH HHS R33 CA281702NCI NIH HHS U54 CA209992NIDA NIH HHS RF1 DA048811NIGMS NIH HHS T32 GM007205U.S. Department of Health & Human Services | National Institutes of Health (NIH) DP2CA238295U.S. Department of Health & Human Services | National Institutes of Health (NIH) F30CA250249U.S. Department of Health & Human Services | National Institutes of Health (NIH) K99CA282989U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA231112U.S. Department of Health & Human Services | National Institutes of Health (NIH) R33CA281702U.S. Department of Health & Human Services | National Institutes of Health (NIH) RF1DA048811U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32GM007205U.S. Department of Health & Human Services | National Institutes of Health (NIH) U54CA209992
Abstract
The pleiotropic effects of human disease and the complex nature of gene-interaction networks require knock-in mice allowing for multiplexed gene perturbations. Here we describe a series of knock-in mice with a C57BL/6 background and with the conditional or constitutive expression of LbCas12a or of high-fidelity enhanced AsCas12a, which were inserted at the Rosa26 locus. The constitutive expression of Cas12a in the mice did not lead to discernible pathology and enabled efficient multiplexed genome engineering. We used the mice for the retrovirus-based immune-cell engineering of CD4
Indexed as
Cell EngineeringCRISPR-Associated ProteinsGene EditingGene Knock-In TechniquesAnimalsBacterial ProteinsCRISPR-Cas SystemsDendritic CellsDependovirusDisease Models, AnimalEndodeoxyribonucleasesHumansMiceMice, Inbred C57BLBacterial ProteinsCas12a proteinCRISPR-Associated ProteinsEndodeoxyribonucleases
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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.