Reducible siRNA Dimeric Conjugates for Efficient Cellular Uptake and Gene Silencing

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In 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.
Publisher
Amer Chemical Soc
Issue Date
2011-01
Language
English
Article Type
Article
Keywords

INTRACELLULAR DELIVERY; VEGF SIRNA; CELLS; RNA; TRANSFECTION; MECHANISMS; DUPLEXES; THERAPY; DISEASE; ACID

Citation

BIOCONJUGATE CHEMISTRY, v.22, no.2, pp.299 - 306

ISSN
1043-1802
URI
http://hdl.handle.net/10203/95640
Appears in Collection
NT-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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