ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 118 citations in OpenAlex.
- RNA Activation in Plants: Current Evidence and Molecular Insights.Plants (Basel, Switzerland) · 2026Review
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Small Activating RNAs: A Curated Database and an Overview of Rational Design Principles.Molecules (Basel, Switzerland) · 2026Review
- Working So Hard: Double-Stranded RNAs That Can Perform Both Gene Activation and Gene Silencing.Chembiochem : a European journal of chemical biology · 2026Article
- Argonaute and small RNAs in the nucleus: Mediators of gene silencing and activation.Molecular therapy. Nucleic acids · 2026Review
- 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
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- RNA activation as a precision dosing modality: MTL-CEBPA for controlled enzyme elevation in MPS I-H.Frontiers in medicine · 2026Article
- RNAa-Mediated Gene Activation in the Regulation of Stem Cell Fate.Biomolecules · 2025Review
- RNA Therapeutics: Delivery Problems and Solutions-A Review.Pharmaceutics · 2025Review
- Small activating RNA AW1-51 (CEBPA-51) elicits targeted DNA demethylation to promote gene activation.bioRxiv : the preprint server for biology · 2025Article
- RNA activation ofMolecular therapy. Nucleic acids · 2025Article
- Integrator Complex Subunit 6 Regulates Biological Nature of Hepatocellular Carcinoma by Modulating Epithelial-Mesenchymal Transition.Current issues in molecular biology · 2025Article
- Upgrading nucleic acid and antisense therapeutics: challenges, solutions, and future directions.Bioanalysis · 2025Review
- Promoter-targeted small RNA duplexes increase MBNL1 transcription and mitigate myotonic dystrophy-associated spliceopathy.Nucleic acids research · 2025Article
- Emerging vesicular nanosystems capable of effectively targeting hepatocytes.Nanomedicine (London, England) · 2025Review
- Phytochemical profiling and anticancer potential of pistachio wastes against MCF-7 breast cancer cells: a metabolic and apoptotic pathway analysis.BMC complementary medicine and therapies · 2025Article
- RNAa: Mechanisms, therapeutic potential, and clinical progress.Molecular therapy. Nucleic acids · 2025Review
- Clinical applications of oligonucleotides for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. A bioinformatically directed nucleotide walk around the CEBPA gene identified an saRNA sequence that upregulates CEBPA mRNA 2.5-fold in human hepatocellular carcinoma cells. A nuclear run-on assay confirmed that this upregulation is a transcriptionally driven process. Mechanistic experiments demonstrate that Argonaute-2 (Ago2) is required for saRNA activity, with the guide strand of the saRNA shown to be associated with Ago2 and localized at the CEBPA genomic locus using RNA chromatin immunoprecipitation (ChIP) assays. The data support a sequence-specific on-target saRNA activity that leads to enhanced CEBPA mRNA transcription. Chemical modifications were introduced in the saRNA duplex to prevent activation of the innate immunity. This modified saRNA retains activation of CEBPA mRNA and downstream targets and inhibits growth of liver cancer cell lines in vitro. This novel drug has been encapsulated in a liposomal formulation for liver delivery, is currently in a phase I clinical trial for patients with liver cancer, and represents the first human study of an saRNA therapeutic.
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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.