Figure 4.

(A) Schematic presentation of the foreseen action of oligonucleotide-based artificial ribonucleases in a therapeutic setting: 1) Cell entry 2) Sequence-dependent hybridization to the RNA target by Watson-Crick base pairing 3) Cleavage of one or several phosphodiester linkages in the RNA target 4) Release of cleaved RNA fragments 5) Finding the next target to repeat the cycle and give substrate turnover. (B) Mechanism of action of RNA‐PROTACs binding RBPs and directing them to degradation. Structure of Lin28 zinc finger domain binding to its consensus sequence AGGAGAU, which was used as ligand for the PROTAC. (Adapted from Ghidini et al [228].) (C) Proposed mode of action of an antibody−PROTAC conjugate, resulting in HER2-dependent protein degradation and its overall structure. (Adapted from Maneiro et al [231].).