RNA Interference

RNAi is a natural process with exquisite specificity for the destruction of messenger RNA (mRNA), and thus control of protein expression. The RNAi pathway is outlined in the figure below.

The RNAi process is initiated when double stranded RNA (dsRNA) such as viral RNA, a transposon, or (microRNA) enters the cellular cytoplasm. When this occurs, Dicer is guided to the dsRNA. Dicer cleaves the dsRNA or shRNA molecules into short interfering (si) RNA fragments of 20 to 25 base pairs in length. The resulting siRNA is incorporated into the RNA-induced silencing complex (RISC) where the duplex is unwound into two strands. One of the strands, termed the passenger strand, is ejected from RISC and degraded by intracellular enzymes. The second strand, termed the guide strand since it "guides" RISC to pair with the targeted mRNA, drives the site-specific cleavage and degradation (i.e., silencing) of the target mRNA, thus "silencing" the gene that codes for the targeted protein via the mRNA intermediate.

RISC-mediated degradation of mRNA silences genes without altering DNA. As the mRNA is degraded, RISC is released to pair with another mRNA target. It is this aspect of RNAi – the catalytic nature whereby one activated RISC can mediate multiple rounds of mRNA degradation – that makes RNAi-based therapeutics ideal for treating diseases characterized by abnormal protein production, and specifically provides advantages over other therapeutics that typically acts on a one-to-one basis.

The RNAi process can be initiated by direct delivery of siRNA into a target cell. Our tauRNAi platform is based on the delivery of highly potent UsiRNAs via our dialkylated amino acid liposome technology. Our tkRNAi platform involves delivery of shRNAs into a target cell via modified bacteria.

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