title: Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice.
abstract: MicroRNAs (miRNAs) are emerging as potential cancer therapeutics, but effective delivery mechanisms to tumor sites are a roadblock to utility. Here we show that systemically delivered, synthetic miRNA mimics in complex with a novel neutral lipid emulsion are preferentially targeted to lung tumors and show therapeutic benefit in mouse models of lung cancer. Therapeutic delivery was demonstrated using mimics of the tumor suppressors, microRNA-34a (miR-34a) and let-7, both of which are often down regulated or lost in lung cancer. Systemic treatment of a Kras-activated autochthonous mouse model of non-small cell lung cancer (NSCLC) led to a significant decrease in tumor burden. Specifically, mice treated with miR-34a displayed a 60% reduction in tumor area compared to mice treated with a miRNA control. Similar results were obtained with the let-7 mimic. These findings provide direct evidence that synthetic miRNA mimics can be systemically delivered to the mammalian lung and support the promise of miRNAs as a future targeted therapy for lung cancer.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Phong
authors.initials: P
authors.lastname: Trang
authors.forename: Jason F
authors.initials: JF
authors.lastname: Wiggins
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Daige
authors.forename: Chris
authors.initials: C
authors.lastname: Cho
authors.forename: Michael
authors.initials: M
authors.lastname: Omotola
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Weidhaas
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Bader
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Slack
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004655:Emulsions / Q000737:chemistry*; D005822:Genetic Vectors / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004655:Emulsions; D008055:Lipids; D035683:MicroRNAs