Gene Silencing by a DNA Vector-Based RNAi Technology

Double-stranded RNA (dsRNA) can suppress gene expression by inducing mRNA degradation of the homologous gene, known as RNA interference (RNAi). First, an RNase III-like dsRNA-specific endonuclease, Dicer, cleaves long dsRNA into 21- to 23-nucleotide (nt) small, interfering RNAs (siRNAs). Second, each resulting siRNA is incorporated into an RNA-induced silencing complex (RISC), which consists of eIF2C1, eIF2C2, Gemin3 (an RNA helicase), Gemin4 and other proteins. The siRNA guides the RISC to the homologous mRNA. Finally, the endoribonuclease in the RISC cleaves the targeted mRNA at the vicinity of the binding site, followed by further degradation of the mRNA by an exoribonuclease. As a result, gene silencing is established.