ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
GalNAc-conjugated siRNA targeting the DNAJB1-PRKACA fusion junction in fibrolamellar hepatocellular carcinoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Article
- Exploring the Link Between Stress-Induced Naive T-Cells and Esophageal Squamous Cell Carcinoma Risk: A Multi-Omics Investigation.Annals of surgical oncology · 2026Article
- Mitochondrial LINC00942 activates complex I and inhibits ferroptosis through interacting with GRSF1 in liver cancer.Science China. Life sciences · 2026Article
- A novel auto-fluorescent porphyrin-lipid nanoparticle strategy for CTNNB1 gene silencing in hepatocellular carcinoma.Frontiers in oncology · 2026Article
- Transforming acidic coiled-coil-containing protein 3-mediated lipid metabolism reprogramming impairs CD8Signal transduction and targeted therapy · 2025Article
- Chemical Evolution of Aplithianine Class of Serine/Threonine Kinase Inhibitors.Journal of medicinal chemistry · 2025Article
- Advances in Lipid-Based Nanomedicine: Pathway Specific siRNA Therapy and Optimizing Delivery for Hepatocellular Carcinoma.International journal of nanomedicine · 2025Review
- Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma.Nature communications · 2024Article
- Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1.Cancer research · 2024Article
- Exosome-mediated delivery of siRNA molecules in cancer therapy: triumphs and challenges.Frontiers in molecular biosciences · 2024Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer caused by a dominant recurrent fusion of the heat shock protein (DNAJB1) and the catalytic subunit of protein kinase A (PRKACA). Current therapies such as chemotherapy and radiation have limited efficacy, and new treatment options are needed urgently. We have previously shown that FLC tumors are dependent on the fusion kinase DNAJB1::PRKACA, making the oncokinase an ideal drug target. mRNA degrading modalities such as antisense oligonucleotides or small interfering RNAs (siRNAs) provide an opportunity to specifically target the fusion junction. Here, we identify a potent and specific siRNA that inhibits DNAJB1::PRKACA expression. We found expression of the asialoglycoprotein receptor in FLC to be maintained at sufficient levels to effectively deliver siRNA conjugated to the GalNAc ligand. We observe productive uptake and siRNA activity in FLC patient-derived xenografts (PDX) models in vitro and in vivo. Knockdown of DNAJB1::PRKACA results in durable growth inhibition of FLC PDX in vivo with no detectable toxicities. Our results suggest that this approach could be a treatment option for FLC patients.
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Registered trials
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