ArticleProceedings of the National Academy of Sciences of the United States of America2016
Versatile in vivo regulation of tumor phenotypes by dCas9-mediated transcriptional perturbation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma.Nature communications · 2025Article
- CRISPR/Cas technologies in pancreatic cancer research and therapeutics: recent advances and future outlook.Discover oncology · 2025Review
- Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies.Oncogene · 2025Review
- Review
- Advances in Making Cancer Mouse Models More Accessible and Informative through Non-Germline Genetic Engineering.Cold Spring Harbor perspectives in medicine · 2024Review
- CPADS: a web tool for comprehensive pancancer analysis of drug sensitivity.Briefings in bioinformatics · 2024Article
- Review
- Knowledge mapping and current trends of global research on CRISPR in the field of cancer.Frontiers in cell and developmental biology · 2023Article
- Tutorial: design and execution of CRISPR in vivo screens.Nature protocols · 2022Review
- Review
- AnCancer discovery · 2022Article
- CRISPR-Based Approaches for the High-Throughput Characterization of Long Non-Coding RNAs.Non-coding RNA · 2021Review
- Integrating Biomaterials and Genome Editing Approaches to Advance Biomedical Science.Annual review of biomedical engineering · 2021Article
- Review
- CRISPR activation screen in mice identifies novel membrane proteins enhancing pulmonary metastatic colonisation.Communications biology · 2021Article
- Targeting cancer epigenetics with CRISPR-dCAS9: Principles and prospects.Methods (San Diego, Calif.) · 2021Review
- Forward and Reverse Genetics of B Cell Malignancies: From Insertional Mutagenesis to CRISPR-Cas.Frontiers in immunology · 2021Review
- CRISPR/Cas: Advances, Limitations, and Applications for Precision Cancer Research.Frontiers in medicine · 2021Review
- In vivo functional screening for systems-level integrative cancer genomics.Nature reviews. Cancer · 2020Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Targeted transcriptional regulation is a powerful tool to study genetic mediators of cellular behavior. Here, we show that catalytically dead Cas9 (dCas9) targeted to genomic regions upstream or downstream of the transcription start site allows for specific and sustainable gene-expression level alterations in tumor cells in vitro and in syngeneic immune-competent mouse models. We used this approach for a high-coverage pooled gene-activation screen in vivo and discovered previously unidentified modulators of tumor growth and therapeutic response. Moreover, by using dCas9 linked to an activation domain, we can either enhance or suppress target gene expression simply by changing the genetic location of dCas9 binding relative to the transcription start site. We demonstrate that these directed changes in gene-transcription levels occur with minimal off-target effects. Our findings highlight the use of dCas9-mediated transcriptional regulation as a versatile tool to reproducibly interrogate tumor phenotypes in vivo.
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