Cationic siRNAs Provide Carrier-Free Gene Silencing in Animal Cells

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• 作者：Marc Nothisen ; Mitsuharu Kotera ; Emilie Voirin ; Jean-Serge Remy ; Jean-Paul Behr
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：December 16, 2009
• 年：2009
• 卷：131
• 期：49
• 页码：17730-17731
• 全文大小：151K
• 年卷期：v.131,no.49(December 16, 2009)
• ISSN：1520-5126

文摘

siRNA-mediated gene silencing requires intracellular delivery of the nucleic acid. We have developed a carrierless molecular approach that follows the same cell entry route as cationic supramolecular complexes, yet should avoid the extracellular barriers encountered by nanoparticles. Cationic oligospermine−oligonucleotide conjugates (ZNAs, for Zip Nucleic Acids) were synthesized stepwise on an oligonucleotide synthesizer using a DMT-spermine phosphoramidite derivative. They were shown to enter cells and have access to the cytoplasm, provided their formal charge ratio N/P was >1.5. Cationic siRNAs that fulfilled this condition were shown to achieve selective inhibition of luciferase gene expression in the submicromolar concentration range in constitutively luciferase-expressing cells.