Reducible siRNA Dimeric Conjugates for Efficient Cellular Uptake and Gene Silencing

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dc.contributor.authorChung, Hyun-Jungko
dc.contributor.authorHong, Cheol-Amko
dc.contributor.authorLee, Soo-Hyeonko
dc.contributor.authorJo, Sung-Dukko
dc.contributor.authorPark, Tae-Gwanko
dc.date.accessioned2013-03-09T06:49:32Z-
dc.date.available2013-03-09T06:49:32Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued2011-01-
dc.identifier.citationBIOCONJUGATE CHEMISTRY, v.22, no.2, pp.299 - 306-
dc.identifier.issn1043-1802-
dc.identifier.urihttp://hdl.handle.net/10203/95640-
dc.description.abstractIn this study, dimerized siRNAs linked by a cleavable disulfide bond were synthesized for efficient intracellular delivery and gene silencing. The reducible dimerized siRNAs showed far enhanced complexation behaviors with cationic polymers as compared to monomeric siRNA at the same N/P ratio, as demonstrated by microscopic techniques and gel characterization. Dimerized siRNAs targeting green fluorescent protein (GFP) or vascular endothelial growth factor (VEGF) were complexed with linear polyethylenimine (LPEI), and treated to various cell lines to examine gene transfection efficiencies. In comparison to monomer siRNA/LPEI complexes, dimeric siRNA/LPEI complexes showed greatly enhanced cellular uptake and gene silencing effects, in vitro. These results Were mainly due to the higher charge density and promoted chain flexibility of the dimerized siRNAs, providing more compact and stable siRNA complexes. In addition, the conjugation strategy of reducible siRNA dimers was further extended: poly(ethylene glycol) (PEG) modified dimerized siRNAs and heterodimers of siRNAs targeting two different genes (e g, GFP and VEGF) were synthesized, and their, gene silencing efficiencies were characterized. The dimerized siRNA complex system holds great potential for in vivo systemic gene therapy.-
dc.languageEnglish-
dc.publisherAmer Chemical Soc-
dc.subjectINTRACELLULAR DELIVERY-
dc.subjectVEGF SIRNA-
dc.subjectCELLS-
dc.subjectRNA-
dc.subjectTRANSFECTION-
dc.subjectMECHANISMS-
dc.subjectDUPLEXES-
dc.subjectTHERAPY-
dc.subjectDISEASE-
dc.subjectACID-
dc.titleReducible siRNA Dimeric Conjugates for Efficient Cellular Uptake and Gene Silencing-
dc.typeArticle-
dc.identifier.wosid000287297000024-
dc.identifier.scopusid2-s2.0-79951704506-
dc.type.rimsART-
dc.citation.volume22-
dc.citation.issue2-
dc.citation.beginningpage299-
dc.citation.endingpage306-
dc.citation.publicationnameBIOCONJUGATE CHEMISTRY-
dc.contributor.localauthorChung, Hyun-Jung-
dc.contributor.localauthorPark, Tae-Gwan-
dc.contributor.nonIdAuthorHong, Cheol-Am-
dc.contributor.nonIdAuthorJo, Sung-Duk-
dc.type.journalArticleArticle-
dc.subject.keywordPlusINTRACELLULAR DELIVERY-
dc.subject.keywordPlusVEGF SIRNA-
dc.subject.keywordPlusCELLS-
dc.subject.keywordPlusRNA-
dc.subject.keywordPlusTRANSFECTION-
dc.subject.keywordPlusMECHANISMS-
dc.subject.keywordPlusDUPLEXES-
dc.subject.keywordPlusTHERAPY-
dc.subject.keywordPlusDISEASE-
dc.subject.keywordPlusACID-
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NT-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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