molecular mechanisms of antisense

An important area of Isis' basic research is to understand the molecular mechanisms of antisense. There are at least 12 known antisense mechanisms that can be exploited once an antisense drug binds to its target RNA. Isis has created proprietary chemical modifications to trigger many of these mechanisms for drug discovery. As its understanding of these mechanisms further improves, the Company expects to develop antisense drugs with enhanced performance and for broader therapeutic applications.

An antisense mechanism is defined as the process in which an antisense drug works after it binds (hybridizes) to a target RNA to form a duplex. The formation of this duplex, or two-stranded molecule, prevents the RNA from functioning normally and from producing a protein product.

Progress in Isis' mechanism of action research program is illustrated by the Company's accomplishments in understanding RNase H. The majority of late-stage antisense drugs in development bind to their target RNA and activate a cellular enzyme called RNase H. This enzyme destroys the target RNA, inhibiting production of a specific protein. Isis has cloned and characterized human RNase H and has effectively used that information to design its proprietary second-generation drugs. The Company expects to further improve its drugs, using its insights into the RNase H mechanism.

In addition to its RNase H expertise, Isis has made advancements in understanding and exploiting other antisense mechanisms.

http://www.isispharm.com/antisenseMechanisms.html