ArticleCancer research2022
A Programmable In Vivo CRISPR Activation Model Elucidates the Oncogenic and Immunosuppressive Functions of MYC in Lung Adenocarcinoma.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 22 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
- CircRNF10 sequestrates β-catenin by a dual regulatory circuit of direct degradation and a miR-1275/DKK3-mediated inhibition in driver gene- negative lung adenocarcinoma.Molecular cancer · 2025Article
- An allele-agnostic mutant-KRAS inhibitor suppresses tumor maintenance signals and reprograms tumor immunity in pancreatic cancer.Science translational medicine · 2025Article
- Beyond the Limit: MYC Mediates Tumor Immune Escape.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Cryopreservation of human lung tissue for 3D ex vivo analysis.Respiratory research · 2025Review
- Translating premalignant biology to accelerate non-small-cell lung cancer interception.Nature reviews. Cancer · 2025Review
- On RNA-programmable gene modulation as a versatile set of principles targeting muscular dystrophies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Advances in Making Cancer Mouse Models More Accessible and Informative through Non-Germline Genetic Engineering.Cold Spring Harbor perspectives in medicine · 2024Review
- Construction of tumor organoids and their application to cancer research and therapy.Theranostics · 2024Review
- Pathogen-driven CRISPR screens identify TREX1 as a regulator of DNA self-sensing during influenza virus infection.Cell host & microbe · 2023Article
- CRISPR-Cas-mediated transcriptional modulation: The therapeutic promises of CRISPRa and CRISPRi.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- High-Throughput Identification, Modeling, and Analysis of Cancer Driver Genes In Vivo.Cold Spring Harbor perspectives in medicine · 2023Review
- Pathogen-driven CRISPR screens identify TREX1 as a regulator of DNA self-sensing during influenza virus infection.bioRxiv : the preprint server for biology · 2023Article
- Applications and advancements of CRISPR-Cas in the treatment of lung cancer.Frontiers in cell and developmental biology · 2023Review
- Applications of CRISPR/Cas technology against drug-resistant lung cancers: an update.Molecular biology reports · 2022Review
- Molecular Mechanisms ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Conventional genetically engineered mouse models (GEMM) are time-consuming, laborious, and offer limited spatiotemporal control. Here, we describe the development of a streamlined platform for in vivo gene activation using CRISPR activation (CRISPRa) technology. Unlike conventional GEMMs, this model system allows for flexible, sustained, and timed activation of one or more target genes using single or pooled lentiviral guides. Myc and Yap1 were used as model oncogenes to demonstrate gene activation in primary pancreatic organoid cultures in vitro and enhanced tumorigenic potential in Myc-activated organoids when transplanted orthotopically in vivo. Implementation of this model as an autochthonous lung cancer model showed that transduction-mediated activation of Myc led to accelerated tumor progression and significantly reduced overall survival relative to nontargeted tumor controls. Furthermore, Myc activation led to the acquisition of an immune suppressive, "cold" tumor microenvironment. Cross-species validation of these results using publicly available RNA/DNA-seq datasets linked MYC to a previously described immunosuppressive molecular subtype in patient tumors, thus identifying a patient cohort that may benefit from combined MYC- and immune-targeted therapies. Overall, this work demonstrates how CRISPRa can be used for rapid functional validation of putative oncogenes and may allow for the identification and evaluation of potential metastatic and oncogenic drivers through competitive screening. SIGNIFICANCE: A streamlined platform for programmable CRISPR gene activation enables rapid evaluation and functional validation of putative oncogenes in vivo.
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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.