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  • Title: Development of a novel nonviral gene silencing system that is effective both in vitro and in vivo by using a star-shaped block copolymer (star vector).
    Author: Mori T, Ishikawa A, Nemoto Y, Kambe N, Sakamoto M, Nakayama Y.
    Journal: Bioconjug Chem; 2009 Jun; 20(6):1262-9. PubMed ID: 19456093.
    Abstract:
    The objective of our study was to develop a novel nonviral gene silencing system using small interfering RNA (siRNA) or short hairpin RNA (shRNA) complexes using star vector (SV), which is a star-shaped, four-branched, cationic-nonionic-blocked copolymer, as the water-soluble delivery system. This vector was previously designed as a carrier for high-efficiency gene delivery of plasmid DNA. The lamin gene was used as the target for developing siRNAs. SV was shown to condense and interact with siRNAs to yield SV/siRNA polyion complexes with a diameter of ca. 90 nm and having considerable stability. By using these complexes, siRNA was successfully delivered to almost all human hepatocellular carcinoma cells used in this study, and both siRNAs and shRNAs could produce significant gene silencing in these cells without affecting cell viability. The silencing efficacy of these complexes was similar to that of commercially available high-efficiency siRNA transfection reagent (Darmafect-4). After injecting SV/siRNA complexes into mice, effective gene silencing was also observed in vivo in the liver and lung, suggesting that the SV/siRNA complexes were stable under in vivo conditions, and their transfection efficiency was retained after intravenous administration. Thus, SV was a potential carrier for siRNA and shRNA delivery in both in vitro and in vivo conditions; this finding suggests that it may offer a new clinical therapeutic approach in gene therapy.
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