In this study, we employ DNA nanotechnology to control PROTAC activity. DNA nanotechnology is ideal for this application due to its remarkable programmability and structural versatility. PROTAC warheads have previously been attached to large DNA tetrahedra for protein degradation, but these are expensive to synthesise, difficult to produce on a large scale, and static in nature . Hybridisation chain reactions have also been used to assemble PROTACs in cells, but this requires complicated delivery procedures involving two separate DNA strands . Here, we have generated oligonucleotide-linked PROTACS (OligoPROTACs) through simple hybridisation of two short DNA strands: one 3'-modified strand with a POI binder and the other 5'-modified with an E3 ligase binder (Figure ). Introducing different numbers of non-complementary base pair arms between the double stranded DNA (dsDNA) region and the warheads enabled us to optimise the spatial positioning of the three-component system (dsDNA/POI/E3 ligase) for enhanced protein degradation. Through incorporation of a toehold sequence into the OligoPROTAC, we demonstrate a dynamic off-switch mechanism for controlling protein degradation activity. This was achieved by incubation with a third inhibitor strand, which disrupts the dsDNA duplex through toehold-mediated strand displacement, thereby separating the PROTAC warheads, causing inactivation, and subsequent recovery of protein levels. This approach can serve as a general mechanism for the precise regulation of PROTAC function. OligoPROTACs utilize a double-stranded DNA linker to present PROTAC warheads, which recruit an E3 ligase to induce ubiquitination and subsequent degradation of a target protein. The system includes a overhang to facilitate a toehold-mediated strand displacement mechanism as an "off" switch for controlling activation.