title: Long double-stranded multiplex siRNAs for dual genes silencing.
abstract: Simultaneous suppression of multiple oncogenes is an attractive strategy to treat cancers. Herein we present a series of long double-stranded multiplex small interfering RNAs (multi-siRNAs) that is suitable for dual genes silencing through a sequence-specific RNA interference process without inducing significant immune responses. A gap feature structurally designed in either of the nucleotide strands of the multi-siRNAs was proved to be essential toward silencing target genes and avoiding immune responses. Furthermore, the silencing effect of multi-siRNAs against SURVIVIN and BCL-2 genes was shown to be effective and resulted in up-regulation of caspase-3 related apoptosis and, in turn, inhibition of bladder cancer cell proliferation. Our observation suggested that the rationally designed multi-siRNAs would have great potential for therapeutic siRNA design.
authors: Biomics Biotechnologies Co., Ltd., Nantong, Jiangsu, China.
authors: Wei
authors: W
authors: Peng
authors: Jianxin
authors: J
authors: Chen
authors: Yinchao
authors: Y
authors: Qin
authors: Zhenjun
authors: Z
authors: Yang
authors: York Yuanyuan
authors: YY
authors: Zhu
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000276:immunology; D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000138:chemical synthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000235:genetics*; D016601:RNA-Binding Proteins; D000077022:Survivin; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C107489:BIRC5 protein, human; D002352:Carrier Proteins; C484290:IFIT1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000077022:Survivin; D007372:Interferons; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D053148:Caspase 3
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