Autotransfecting Short Interfering RNA through Facile Covalent Polymer Escorts

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• 作者：Saadyah E. Averick ; Eduardo Paredes ; Sourav K. Dey ; Kristin M. Snyder ; Nikos Tapinos ; Krzysztof Matyjaszewski ; Subha R. Das
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：August 28, 2013
• 年：2013
• 卷：135
• 期：34
• 页码：12508-12511
• 全文大小：249K
• 年卷期：v.135,no.34(August 28, 2013)
• ISSN：1520-5126

文摘

Short interfering ribonucleic acids (siRNAs) are important agents for RNA interference (RNAi) that have proven useful in gene function studies and therapeutic applications. However, the efficacy of exogenous siRNAs for gene knockdown remains hampered by their susceptibility to cellular nucleases and impermeability to cell membranes. We report here new covalent polymer-escort siRNA constructs that address both of these constraints simultaneously. By simple postsynthetic click conjugation of polymers to the passenger strand of an siRNA duplex followed by annealing with the complementary guide strand, we obtained siRNA in which one strand includes terminal polymer escorts. The polymer escorts both confer protection against nucleases and facilitate cellular internalization of the siRNA. These autotransfecting polymer-escort siRNAs are viable in RNAi and effective in knocking down reporter and endogenous genes.