Isis Pharmaceuticals Inc. scientists reported on the relationship between the structureof an RNA target and the ability of an antisense drug molecule to bind to that target in arecent issue of the journal Biochemistry, the Carlsbad, Calif., company(NASDAQ:ISIP) said.
Researcher Walt Lima and associates found that antisense compounds designed on thebasis of target RNA structure can distinguish the RNA for a normal ras gene from that fora mutant form of the gene, termed Ha-ras, that is associated with a number of differentcancers. These two messenger RNA's differ by only a single base change, or point mutation,but “that point mutation is in the stem loop structure of the RNA molecule,“explained Christopher Mirabelli, Isis' senior vice president of research and preclinicaldevelopment.
And it has become apparent that the often complex three-dimensional structures of viraland cellular RNAs can interfere with the adequate binding of antisense drug molecules,even if they are designed to exactly complement the target RNA sequence.
The experiments reflect a rational approach to designing a compound that applies rulesregarding RNA secondary structure to the target molecule, as well as being able toselectively target a single point mutation, Mirabelli said.