CARB 2 |
| RNA interference (RNAi) is a powerful biological process for specific silencing of mRNAs in diversified eukaryotic cells. By introducing chemical modifications into synthetic siRNA building blocks, desirable "drug-like" properties can be imparted to the siRNAs. siRNAs containing chemical modifications show enhanced resistance towards degradation, as well as reduced "off-target" effects. To achieve in vivo delivery, certain chemical conjugates and novel formulations are being investigated. Alnylam is filling a preclinical and clinical pipeline with RNAi-based therapeutics to treat respiratory diseases, cancer, and a broad range of other diseases, including metabolic and neurologic disorders. Alnylam's most advanced program deals with the development of a siRNA for the treatment of respiratory syncytial virus (RSV) infection. In the systemic treatment arena, we have demonstrated the ability to silence several liver gene targets, including PCSK9, that are important in metabolic diseases. PCSK9 has been genetically and experimentally implicated in LDLc regulation. We have shown in several animal models that silencing of PCSK9 in liver by systemically delivered siRNA lowers both circulating PCSK9 protein levels in blood and plasma cholesterol levels. In the oncology area, we are developing a therapeutic for hepatocelluar carcinoma (HCC) comprising siRNAs targeting VEGF and the mitotic kinesin, KSP (Kif11). Our progress in each of these programs will be discussed. |
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RNA as a Drug Target
8:20 AM-1:20 PM, Sunday, April 6, 2008 Morial Convention Center -- Rm. 214, Oral
Division of Carbohydrate Chemistry |