title: Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.
abstract: miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR34a targets. The administration of the formulated miR34a mimic caused significant tumor growth inhibition in both models of liver cancer, and tumor regression was observed in more than one third of the animals. The antitumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers.
authors: Mirna Therapeutics, Inc., Austin, Texas.
authors: Christopher L
authors: CL
authors: Daige
authors: Mirna Therapeutics, Inc., Austin, Texas.
authors: Jason F
authors: JF
authors: Wiggins
authors: Mirna Therapeutics, Inc., Austin, Texas.
authors: Leslie
authors: L
authors: Priddy
authors: Mirna Therapeutics, Inc., Austin, Texas.
authors: Terri
authors: T
authors: Nelligan-Davis
authors: Mirna Therapeutics, Inc., Austin, Texas.
authors: Jane
authors: J
authors: Zhao
authors: Mirna Therapeutics, Inc., Austin, Texas. dbrown@mirnarx.com.
authors: David
authors: D
authors: Brown
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000008:administration & dosage* / Q000009:adverse effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger