siRNAs with decreased off-target effect facilitate the identification of essential genes in cancer cells

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	siRNAs with decreased off-target effect facilitate the identification of essential genes in cancer cells
	Li, CY; Liu, ZZ; Yang, F; Liu, WS; Wang, D; Dong, EC; Wang, Y; Wu, CI; Lu, XM
	2015
发表期刊	ONCOTARGET
ISSN	1949-2553
卷号	6 期号:25 页码:21603-21613
摘要	Since the essential genes are crucial to the proliferation and survival of cancer cells, the interference of these genes is promising to be an option for cancer therapy to overcome heterogeneity. However, the essential genes are highly overestimated by RNA interference (RNAi) screenings, which is mainly caused by the pervasive off-target effect of small interference RNA (siRNA) and short hairpin RNA (shRNA). In the present study, we designed Match-Mismatch paired siRNAs to discriminate the on-target effect from off-target effect of siRNAs on cell viability. Only one of the 7 potential essential genes was validated as essential to cell viability, which demonstrates the high false positive rate in RNAi screenings. We modified the siRNA by introducing random nucleotides (N) into the guide strand to mitigate the off-target effect, without significantly compromising the on-target effect. The whole transcriptome profile analysis of cells transfected with siRNAs with or without N indicates that siRNA-dN (with Ns on both the 2nd and the 18th bases of the guide strand) weakens the off-target effect by decreasing the unintended targets. The optimized siRNAs can be applied in the characterization of essential genes in cancer cells.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13656
专题	个人在本单位外知识产出
推荐引用方式 GB/T 7714	Li, CY,Liu, ZZ,Yang, F,et al. siRNAs with decreased off-target effect facilitate the identification of essential genes in cancer cells[J]. ONCOTARGET,2015,6(25):21603-21613.
APA	Li, CY.,Liu, ZZ.,Yang, F.,Liu, WS.,Wang, D.,...&Lu, XM.(2015).siRNAs with decreased off-target effect facilitate the identification of essential genes in cancer cells.ONCOTARGET,6(25),21603-21613.
MLA	Li, CY,et al."siRNAs with decreased off-target effect facilitate the identification of essential genes in cancer cells".ONCOTARGET 6.25(2015):21603-21613.

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