siRNAs with a Universal Base

CARB 42

Kallanthottathil G. Rajeev, rajeevk@alnylam.com, Jie Xia, jxia@alnylam.com, Tatiana Novobrantseva, tnovobranseva@alnylam.com, Svetlana Shulga Morskaya, sshuglamorskaya@alnylam.com, Rajendra K. Pandey, rpandey@alnylam.com, Anke Geick, ageick@alnylam.com, Tony De Fougerolles, tdefourgerolles@alnylam.com, Zak Zimmerman, zzmmerman@alnylam.com, and Muthiah Manoharan, mmanoharan@alnylam.com. Alnylam Pharmaceuticals, 300 Third St, Cambridge, MA 02142
Universal or degenerative nucleobase modification was introduced into siRNA. A universal base that allows complementary base pairing with all four natural bases was introduced into the guide strand of an siRNA and its gene silencing efficiency was tested in vitro. Synthesis of monomers and RNA oligonucleotides containing the universal base will be described. The effects of incorporation of the universal base at a number of positions on the guide strand on in vitro siRNA gene silencing will be presented.