We then decided to test whether, following knockdown of BRD4 with the toehold OligoPROTAC [n = 3], toehold-mediated strand displacement could dynamically turn the OligoPROTAC "off" and restore BRD4 levels within the cells. To do this, we first transfected the HEK293T cells with the toehold OligoPROTAC [n = 3] and incubated for 12 hours. We then transfected the anti-toehold complement, the scrambled anti-toehold complement, or no extra DNA, and incubated for an additional 12 hours and harvested protein samples at 24 hours. To our excitement, compard to adding no extra DNA, the antitoehold complement was able to restore BRD4 levels, thereby turning 'off' the OligoPROTAC (Figure , SI Figure ). This effect was again sequence-specific, as the scrambled anti-toehold complement showed no restoration of BRD4 protein levels, therefore no inhibition of the OligoPROTAC activity. These experiments demonstrated that the loss of OligoPROTAC activity, i.e. the 'off' switch, was due to the sequence-specific toehold mediated strand displacement reaction occurring within the cells. Thus, we demonstrate the first instance of a sequence-specific "off" switch for controlling PROTAC activity.