Monday, January 7, 2013

Single-Stranded RNA's can also silence mRNA.

Single-Stranded RNA's Use RNAi to Potently and Allele-Selectively Inhibit Mutant Huntingtin Expression
Dongbo Yu, and Hannah Pendergraff and David R. Corey 
Cell (2012), 150, 895-908

Figuring out the principles of the RNA interference pathway resulted in Craig Mello and Andy Fire getting the nobel prize in medicine in 2006. They found out that double stranded RNA's could interfere the translation of mRNA's sequences. Now it has been found that single-stranded RNA's can work as well as double-stranded RNA's do.
Corey's group claim is: "Our results demonstrate that ss-siRNAs can mimic miRNA's to allele-selectively suppress translation and inhibit mutant HTT expression with potencies and allele selectivities that are at least equal to those possessed by duplex RNAs and ASOs".

Nonetheless there is a potential pitfall to the technique pointed out by Beverly L. Davidson and Alex Mas Monteys in the articles preview:
"The antisense strand can still pose this risk, however, a concern that was not addressed in the current studies. Given the high doses delivered for reduction of target mRNAs in vivo, off-target gene silencing via miRNA-like mechanisms will require careful evaluation. For example, the CAG-repeat-targeting constructs used by Corey and colleagues (Yu et al., 2012), which show selectivity for mutant huntingtin over wild-type huntingtin, use ss-siRNAs with putative seed sequences that could silence numerous other transcripts that do not necessarily contain the full complement of the ss-siRNA."

They also include a nice graphic which illustrates the full panorama of gene-silencing via interference and where the new ssRNAi comes in.




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