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Cationic Nanostructured Polymers for siRNA Delivery in Murine Calvarial Pre-Osteoblasts

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The endogenous RNA interference (RNAi) pathway enables control of pathologies caused by the dysregulation of proteins. Several biological molecules are active in RNAi including short interfering ribonucleic acid (siRNA). The effective utilization of siRNA as a therapeutic agent has been marked with distinct challenges, namely in intracellular delivery and achieving a sufficient dosage to affect protein expression. A delivery strategy we have developed to improve safety and efficacy of siRNA includes complexing siRNA with nanostructured polymers delivery systems (NSPs). These NSPs are synthesized via atom transfer radical polymerization (ATRP) and combine several important advances in polymer architecture for siRNA delivery. This includes shielding the cationic charge of the NSP with a poly(ethylene glycol) (PEG) shell to promote cell viability in MC3T3-E1.4 pre-osteoblasts, and minimize the inflammatory response in a C57BL/6 mouse model. In our gene knockdown experiments targeting glyceraldehyde 3-phosphate dehydrogenase Gapdh expression, star polymer and nanogel polyplexes suppressed Gapdh mRNA to levels comparable to cells treated with Lipofectamine® RNAiMAX lipoplexes.
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Keywords: ATRP; GAPDH KNOCKDOWN; NANOGEL; NANOSTRUCTURED POLYMER; SIRNA DELIVERY; STAR POLYMER

Document Type: Research Article

Publication date: June 1, 2014

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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