Figure 1. Aptamer-mediated siRNA internalization.
Upon binding of the aptamer portion of the conjugate to the target T cell-surface receptor (Step 1), the complex is internalized (Step 2), likely through clathrin-mediated endocytosis. The complex is presumably shuttled through the early, sorting and late endosome (Step 3). To be loaded into the RNAi machinery, the aptamer–siRNA conjugate must escape the endosome (Step 4). The aptamer–siRNA conjugate is recognized by the RNAi machinery (Step 5) and mediates silencing of the target mRNA.