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Teratology Society Symposium Abstracts


Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
118 KB
Volume
70
Category
Article
ISSN
1542-0752

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โœฆ Synopsis


Short-interfering RNAs (siRNAs) are potent sequence-specific reagents designed to suppress gene expression. By systematically analyzing panels of randomly generated functional and nonfunctional siRNA duplexes, as well as naturally occurring miRNAs, we have identified several physical and sequence-related characteristics that affect key steps in RISC-mediated mRNA turnover. We have combined these parameters into our SMART selectionโ„ข algorithm, for guiding rational siRNA design. The algorithm effectively predicts highly functional siRNA sequences and eliminates those that are non-functional. Silencing effectiveness is further improved by pooling the selected siRNA into SMART pool ยฎ reagents. SMART selection and SMART pool technologies enable functional siRNAs to be designed against any gene. Recently at Dharmacon we have introduced our ON-TARGET siRNA where we further increase the specificity of RNAi by introducing modifications to the siRNA that eliminate sense strand mediated off-target effects as determined by microarray-based whole transcritptome profiling. Continuing innovations at Dharmacon are directed toward enabling researchers to expand their studies beyond cultured cells to whole animal systems. In particular, we have developed siSTABLE, a chemical modification strategy that increases siRNA half-life in serum from seconds to days. Rational design and the use of stabilized siRNA duplexes provides a generally useful mechanism for reducing expression of any target gene in biological systems and accelerates critical investigations across a broad range of biomedical and biological research. Accordingly, we are now combining our algorithm-based and chemical modification strategies with siGENOME our recently announced complete human transcriptome library to integrate in vitro and in vivo target discovery and validation with therapeutic siRNA development in a single reagent set.


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