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Biotech / Medical : Ionis Pharmaceuticals (IONS) -- Ignore unavailable to you. Want to Upgrade?

To: Doc Bones who wrote (3428)	5/8/2003 1:06:49 PM
From: tuck	Respond to of 4676

Actually, I think it was more of a foul tip into the catcher's mitt, resulting in an out in one swing. For, if anything, ISIS seems intent on promoting antisense as equal to siRNA mediated gene silencing. >>J Biol Chem 2003 Feb 28;278(9):7108-18 Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. A comparative analysis. Vickers TA, Koo S, Bennett CF, Crooke ST, Dean NM, Baker BF. GeneTrove Division and Antisense Core Research Department, Isis Pharmaceuticals, Inc., Carlsbad, California 92008, USA. tvickers@isiph.com RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays.<< Cheers, Tuck