RNA interference (RNAi) in hematology.

ABSTRACT

RNA interference (RNAi), an evolutionary highly conserved process of post-transcriptional gene silencing, can be triggered by small interfering RNAs (siRNAs) that mediate sequence-specific mRNA degradation. Since the first reports in 1998, RNAi has rapidly been developed into an effective tool to specifically knock down gene expression in a wide variety of target cells. Accordingly, RNAi is currently used for both systematic functional genomics in several organisms and for specific therapeutic intervention in preclinical models of different diseases characterized by aberrant gene expression. However, since siRNAs are not replicated in mammalian cells during the process of RNAi, kinetic aspects of RNAi-induced gene silencing that eventually depend on the intracellular level of siRNA must be considered for each analytical or therapeutic application in these cells. We summarize here some aspects of siRNA design and delivery, of RNAi kinetics, potential side effects, and limitations of siRNA-mediated gene silencing, as well as putative RNAi targets for functional and/or therapeutic intervention in hematopoietic cells.