期刊
CURRENT TOPICS IN MEDICINAL CHEMISTRY
卷 9, 期 12, 页码 1109-1116出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156802609789630884
关键词
Delivery; oligonucleotide; RNAi; endoplasmatic reticulum; intracellular release
The efficient delivery of biologically functional short interfering RNA (siRNA) in vivo remains a widely unresolved technical problem in therapeutic drug development. The repertoire of concepts for the cellular uptake of oligonucleotide-based tools and drugs has been extended by the mechanistically novel finding that phosphorothioate (PS)modified single-stranded oligodeoxyribonucleotides (ON) promote the intracellular accumulation of naked extra-cellular siRNA in a variety of cell types. This mode of delivery gives rise to substantial intracellular amounts of siRNA, up to 10 4 siRNA molecules per cell. Conversely, the moderate biological effectiveness strongly indicates that intracellular release of siRNA from sub-cellular compartments where it seems to be trapped is a necessary step towards efficient target suppression. Here, we summarize key characteristics of the PS-stimulated cellular uptake of siRNA and describe concepts for the increase of intracellular delivery of biologically functional siRNA.
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