To test our 'off' switch in cells, we synthesised the new extended 3'-(+)-JQ1 OligoPROTAC strand containing an 8-base pair toehold sequence at the 5'-end (SI Figure ). This was annealed to the previous 5'-VH032 OligoPROTAC strand, which produced a dsDNA construct with 8 bases of ssDNA on one end (8-base pair toehold), and the (+)-JQ1 and VH032 ligands on [n = 3] arms at the other end (Figure ). This toehold OligoPROTAC [n = 3] was transfected into HEK293T cells and resultant BRD4 degradation was measured by western blotting at 12 hours. As expected, the 8-base pair toehold made no difference to the efficacy of BRD4 degradation with the toehold OligoPROTAC [n = 3], giving comparable efficiency to the previous OligoPROTAC [n = 3]. To turn off the BRD4 degradation in cells, separate lipid nanoparticles containing the Lipofectamine 2000/toehold OligoPROTAC [n = 3] and Lipofectamien 2000/anti-toehold complement strand were co-transfected into HEK293T cells. This was to ensure that the toehold mediated strand displacement would only occur inside the cell, following successful transfection of both nanoparticle species. We attempted the co-transfection with 1:1 and 1:3 ratios for toehold OligoPROTAC [n=3]:anti-toehold complement. Excitingly, upon co-transfection with the anti-toehold complement strand, the degradation activity of the OligoPROTAC was lost (Figure , SI Figure ). This was observed for both ratios of anti-toehold complement. When co-transfecting a scrambled version of the anti-toehold complement strand (in the same ratios), protein degradation was still observed.