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- W2032093175 abstract "Small interfering RNA (siRNA) is a promising biological strategy for treatment of diverse diseases, but the therapeutic application of siRNA has been limited by its instability and poor cellular uptake efficiency. Although the development of various gene delivery systems has increased the siRNA delivery efficiency, many problems still remain to be resolved before the clinical application of siRNA. In this study, we suggest reducible polymerized siRNA a possible solution for low delivery efficiency of siRNA. Dithiol-modified red fluorescent protein (RFP) siRNAs at the 5'-ends of both sense and anti-sense strands were disulfide-polymerized. Polymerized siRNA (poly-siRNA) was composed of 30% oligomeric siRNA (50 approximately 300 bps) and 66% polymeric siRNA (above approximately 300 bps) as fractions, and was reducible in reducing solution through disulfide bond cleavage. Poly-siRNA formed more condensed and nano-sized complexes with low molecular weight polyethylenimine (PEI) by strong electrostatic interaction based on the higher charge density of poly-siRNA, compared with siRNA (mono-siRNA). The compact poly-siRNA/PEI complexes prevented the loss and degradation of siRNA from a polyanion competitor and RNases in serum. Furthermore, poly-siRNA/PEI complexes exhibited superior intracellular uptake by murine melanoma cells (B16F10), and was accompanied with RFP gene silencing efficiency of about 80%, compared to untreated cells. These results sufficiently support that strong polyanionic and reducible poly-siRNA can be utilized as a novel powerful therapeutic strategy for human diseases." @default.
- W2032093175 created "2016-06-24" @default.
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- W2032093175 date "2010-02-15" @default.
- W2032093175 modified "2023-10-16" @default.
- W2032093175 title "Stability and cellular uptake of polymerized siRNA (poly-siRNA)/polyethylenimine (PEI) complexes for efficient gene silencing" @default.
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- W2032093175 doi "https://doi.org/10.1016/j.jconrel.2009.10.007" @default.
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