2012..get set now, page-3

Antisense drugs are short, chemically-modified complementary nucleotide chains that bind to a specific complementary area of mRNA thereby inhibiting translation (protein production) enacted by the ribosome complex. By inhibiting the production of proteins involved in disease, antisense drugs can create therapeutic benefits for patients. There are several types of antisense drugs that can be developed. In fact, Isis scientists know of at least 12 different mechanisms that can be exploited once an antisense drug binds to its target RNA. The differences stem from the enzymes that cleave the RNA complex. Two important mechanisms that have received significant investor attention are small interference RNA (siRNA) and RNA interference (RNAi). Isis is collaborating with partners such as Alnylam Pharmaceuticals and Eli Lilly to explore the potential of both siRNA and RNAi therapeutics.

Antisense drugs have several specific advantages over traditional protein or small-molecule derived therapeutics. Firstly, antisense drugs are highly specific and bind to only the complimentary mRNA strain that codes for the specific protein being targeted. This has the potential to greatly reduce unwanted side-effects that occur through secondary mechanisms of action. Secondly, since all proteins are coded by mRNA, antisense drugs have the potential to work on a broad number of diseases including cardiovascular, metabolic, inflammatory, ocular, viral, neurodegenerative disease, and cancer. Finally, because all antisense drugs start with the basic hybridization of mRNA targets, development timelines are shortened and response is often predictable in the early-stage of development. Sciences need only choose a specific protein to target and then create a small antisense molecule to bind to the transcribed mRNA. This creates efficiency in drug discovery and time to market.

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