Dicerna: Going long in RNAi

Most work in RNAi has been focused on short, double-stranded RNA no more than 23 nucleotides in length because it was thought that longer molecules would have reduced activity. Dicerna Pharmaceuticals Inc. believes its longer oligonucleotides, called Dicer substrates, can provide greater potency and a longer duration of action than short interfering RNA. Perhaps more importantly, the extra nucleotides may help the company solve the systemic delivery problems that have so far dogged RNAi.

Co-founder and CEO Jim Jenson attributes the potency of the Dicer substrates to the manner in which they enter the RNAi pathway. The molecules are 25 or more nucleotides long and target the Dicer enzyme. The enzyme cleaves them into siRNA that becomes integrated into the RNA-induced silencing complex (RISC). RISC uses the bound siRNA molecule to identify complementary mRNA, which the complex then cleaves...