Lee, Seung-Young Huh, Myung Sook Lee, Seulki Lee, So Jin Chung, Hyunjin Park, Jae Hyung Oh, Yu-Kyoung Choi, Kuiwon Kim, Kwangmeyung Kwon, Ick Chan 2024-01-20T20:00:37Z 2024-01-20T20:00:37Z 2021-09-02 2010-02-15 0168-3659 https://pubs.kist.re.kr/handle/201004/131711 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 similar to 300 bps) and 66% polymeric siRNA (above similar to 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. (C) 2009 Elsevier B.V. All rights reserved. English ELSEVIER SMALL INTERFERING RNA DNA TRANSFECTION DELIVERY POLYETHYLENIMINE NANOPARTICLES EXPRESSION CONJUGATE VECTOR CELLS Stability and cellular uptake of polymerized siRNA (poly-siRNA)/polyethylenimine (PEI) complexes for efficient gene silencing Article 10.1016/j.jconrel.2009.10.007 1 JOURNAL OF CONTROLLED RELEASE, v.141, no.3, pp.339 - 346 JOURNAL OF CONTROLLED RELEASE 141 3 339 346 scie scopus 000275569600009 2-s2.0-75549089094 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article SMALL INTERFERING RNA DNA TRANSFECTION DELIVERY POLYETHYLENIMINE NANOPARTICLES EXPRESSION CONJUGATE VECTOR CELLS siRNA Polymerized siRNA Polyethylenimine Electrostatic complexes Gene silencing