An Effective Method for Selecting siRNA Target Sequences in Mammalian Cells

Takasaki, Shigeru; Kotani, Shunsuke; Konagaya, Akihiko

doi:10.4161/cc.3.6.892

Cited by 76 publications

(59 citation statements)

References 46 publications

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“…Earlier analysis by Truss et al [24] indicated a strong preference for GC bases at position 1 which is accord with the observations of Takasaki et al [14], Reynolds et al [15], and Ui-Tei et al [16]. Although the combined probability of G/C occurring in position 1 is high, the occurrence of G chiefly dominates at this position for the OsiRNAs as well as RsiRNAs (Fig.…”

Section: Set1supporting

confidence: 89%

“…Gene silencing by RNA interference attempts to keep detrimental proteins from harming the body by suppressing their expression. The role of siRNAs in gene silencing has been found to be largely effective in Arabidopsis thaliana, Drosophila melanogaster, Caenorhabditis elegans and mammals [12][13][14]. The exclusive selectivity and easy application to virtually any therapeutic target including intracellular factors and transcription factors renders siRNA oligonucleotide applications very promising.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

DSTHO: Database of siRNAs targeted at human oncogenes: A statistical analysis

Dash

Moharana

Reddy

et al. 2006

International Journal of Biological Macromolecules

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Section: Set1supporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

DSTHO: Database of siRNAs targeted at human oncogenes: A statistical analysis

Dash

Moharana

Reddy

et al. 2006

International Journal of Biological Macromolecules

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“…The enrichment in A/U at the 3 0 end of the siRNA and specifically at position 19 has been demonstrated biochemically in the Zamore laboratory to allow better incorporation in the RISC complex (Schwarz et al 2003). This has been confirmed by statistical analysis of the thermodynamical profiles of existing miRNA sequences (Khvorova et al 2003) and several other statistical studies (Amarzguioui and Prydz 2004;Hsieh et al 2004;Reynolds et al 2004;Takasaki et al 2004;Ui-Tei et al 2004). A recent study by Chalk et al (2004) also suggests that the two regions from positions 15 to 19 and from positions 5 to 9 are statistically important regions.…”

Section: Discussionmentioning

confidence: 75%

Sequence characteristics of functional siRNAs

Jagla¹,

Aulner²,

Kelly³

et al. 2005

RNA

140

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RNA interference in mammalian cells is actively used to conduct genetic screens, to identify and to validate targets, and to elucidate regulators and modifiers of cellular pathways. To ensure the specificity and efficacy of the active 21mer siRNA molecules, it is pertinent to develop a strategy for their rational design. Here we show that most functional siRNAs have characteristic sequence features. We tested 601 siRNAs targeting one exogenous and three endogenous genes. The efficacy of the siRNAs was determined at the protein level. Using a decision tree algorithm in combination with information analysis, our analyses revealed four sets of rules with a mean knockdown efficacy ranging from 60% to 73%. (To distinguish between percentages used to describe the quality of an siRNA and the percentages used to describe parts of data sets we underlined the former throughout this paper.) The best rule comprises an A/U at positions 10 and 19, a G/C at position 1, and more than three A/Us between positions 13 and 19, in the sense strand of the siRNA sequence. Using these rules, there is a 99.9% chance of designing an effective siRNA in a set of three with more than 50% knockdown efficiency in a biological readout.

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“…The constraint of the secondary structure of the target mRNA has been shown to influence the activity of both ASOs and siRNAs [20][21][22]. Recently, some approaches have yielded results that further demonstrate the importance of the target structure and its accessibility for the function of the siRNAs [23,24].…”

Section: Introductionmentioning

confidence: 99%