ArticleHepatology (Baltimore, Md.)2018
Combinatorial genetics in liver repopulation and carcinogenesis with a in vivo CRISPR activation platform.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 81 citations in OpenAlex.
- A high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo.Science advances · 2026Article
- An autochthonous CRISPR activation screening platform for characterizing tissue-specific oncogene selection.Cell reports. Medicine · 2026Article
- CRISPR Screening in Hepatocellular Carcinoma: From Tumor Progression to Immune Evasion and Therapeutic Resistance.International journal of molecular sciences · 2026Review
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- Methods and applications of in vivo CRISPR screening.Nature reviews. Genetics · 2025Review
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- Massively parallel in vivo Perturb-seq screening.Nature protocols · 2025Review
- Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications.Cell chemical biology · 2024Review
- Exploring plant-derived phytochrome chaperone proteins for light-switchable transcriptional regulation in mammals.Nature communications · 2024Article
- Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.Frontiers in genome editing · 2024Review
- Transgenerational Epigenetic DNA Methylation Editing and Human Disease.Biomolecules · 2023Review
- CRISPR-Cas-mediated transcriptional modulation: The therapeutic promises of CRISPRa and CRISPRi.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- A Therapeutically Targetable TAZ-TEAD2 Pathway Drives the Growth of Hepatocellular Carcinoma via ANLN and KIF23.Gastroenterology · 2023Article
- CRISPR screens for functional interrogation of immunity.Nature reviews. Immunology · 2023Review
- MYC Overexpression Drives Immune Evasion in Hepatocellular Carcinoma That Is Reversible through Restoration of Proinflammatory Macrophages.Cancer research · 2023Article
- Review
- CRISPR activation and interference as investigative tools in the cardiovascular system.The international journal of biochemistry & cell biology · 2023Article
- Qinggan Huoxue Recipe Protects against Experimental Alcoholic Liver Fibrosis through CXCL16 Inhibition.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- MYC and MET cooperatively drive hepatocellular carcinoma with distinct molecular traits and vulnerabilities.Cell death & disease · 2022Article
- Application of CRISPR for In Vivo Mouse Cancer Studies.Cancers · 2022Review
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10 authors at 2 institutions in 1 country.
Funding
Abstract
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 activation (CRISPRa) systems have enabled genetic screens in cultured cell lines to discover and characterize drivers and inhibitors of cancer cell growth. We adapted this system for use in vivo to assess whether modulating endogenous gene expression levels can result in functional outcomes in the native environment of the liver. We engineered the catalytically dead CRISPR-associated 9 (dCas9)-positive mouse, cyclization recombination-inducible (Cre) CRISPRa system for cell type-specific gene activation in vivo. We tested the capacity for genetic screening in live animals by applying CRISPRa in a clinically relevant model of liver injury and repopulation. We targeted promoters of interest in regenerating hepatocytes using multiple single guide RNAs (gRNAs), and employed high-throughput sequencing to assess enrichment of gRNA sequences during liver repopulation and to link specific gRNAs to the initiation of carcinogenesis. All components of the CRISPRa system were expressed in a cell type-specific manner and activated endogenous gene expression in vivo. Multiple gRNA cassettes targeting a proto-oncogene were significantly enriched following liver repopulation, indicative of enhanced division of cells expressing the proto-oncogene. Furthermore, hepatocellular carcinomas developed containing gRNAs that activated this oncogene, indicative of cancer initiation events. Also, we employed our system for combinatorial cancer genetics in vivo as we found that while clonal hepatocellular carcinomas were dependent on the presence of the oncogene-inducing gRNAs, they were depleted for multiple gRNAs activating tumor suppressors.
conclusionThe in vivo CRISPRa platform developed here allows for parallel and combinatorial genetic screens in live animals; this approach enables screening for drivers and suppressors of cell replication and tumor initiation. (Hepatology 2017).
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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.