RNA interference (RNAi) technology has developed rapidly as a powerful tool for functional genomic analysis and target validation.Due to its potential for highly specific targeted effects in vivo,there is significant interest in using RNAi as therapeutic agents in metabolic diseases,cancer,AIDS,malaria,neurodegenerative disorders,dental diseases and other illnesses.Unmodified siRNA is able to satisfy most laboratory research needs;however,therapeutic applications of unmodified siRNA in vivo are much less effective mainly due to the its rapid degradation in blood and elimination by excretion.Given these observations,developing methods for improving siRNA biochemical and biophysical properties in vivo is important for exploiting siRNA based therapeutic applications.Chemically modified siRNA duplexes with enhanced delivery and improved pharmacokinetics properties are required for therapeutic applications.This presentation,will describe (1) RNA monomers with dual modification chemistries for synthesizing modified siRNAs;(2)the pharmaceutical and biological properties of modified siRNA,and (3) the high potency modified-siRNA gene silencing in vitro and in vivo.