In Vivo Delivery of Cytoplasmic RNA Virus-derived miRNAs
| Autor: | Ryan A. Langlois, Jillian S. Shapiro, Alissa M. Pham, Benjamin R. tenOever |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cytoplasm
Small RNA RNA-induced silencing complex Genetic Vectors Trans-acting siRNA Biology Cell Line Mice Gene Order Drug Discovery microRNA Genetics Animals Humans RNA Viruses RNA-Induced Silencing Complex Gene silencing Molecular Biology Mice Knockout Pharmacology Mice Inbred BALB C Gene knockdown Gene Transfer Techniques RNA Molecular biology Cell biology MicroRNAs RNA silencing Argonaute Proteins Molecular Medicine Original Article |
| Zdroj: | Molecular Therapy. 20:367-375 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2011.244 |
| Popis: | The discovery of microRNAs (miRNAs) revealed an unappreciated level of post-transcriptional control used by the cell to maintain optimal protein levels. This process has represented an attractive strategy for therapeutics that is currently limited by in vivo delivery constraints. Here, we describe the generation of a single-stranded, cytoplasmic virus of negative polarity capable of producing functional miRNAs. Cytoplasmic RNA virus-derived miRNAs accumulated to high levels in vitro, generated significant amounts of miRNA star strand, associated with the RNA-induced silencing complex (RISC), and conferred post transcriptional gene silencing in a sequence-specific manner. Furthermore, we demonstrate that these vectors could deliver miRNAs to a wide range of tissues, and sustain prolonged expression capable of achieving measurable knockdown of physiological targets in vivo. Taken together, these results validate noncanonical processing of cytoplasmic-derived miRNAs and provide a novel platform for small RNA delivery. |
| Databáze: | OpenAIRE |
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