Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents

Figure 1

Antisense mechanism. A schematic representation is shown for two dominant mechanisms by which AS ODN molecules delivered into cells can suppress gene expression. The AS ODN must first anneal to an accessible region of the target mRNA. The first and likely dominant mechanism of inhibition is through recruitment of RNaseH (green) to cleave the RNA is the center of the ODN: Target RNA hybrid region. The second mechanism involves physical hindrance of biochemical processes operative on the mRNA such as ribosome- (violet-) mediated translation, 5′ decapping, and 3′ deadenylation. Here, the hybridized ODN is depicted blocking the progress of translating ribosomes on the mRNA.