PROTACs represent a promising class of targeted protein degradation technologies, but their clinical applications are limited by off-target effects and toxicity. Thus, there is a need to develop methods to fine tune their activity. To address these challenges, we present OligoPROTACs: containing PROTAC warheads positioned in space by a short dsDNA linker. DNA nanotechnology will enable the introduction of unparalleled programmability and versatility into PROTACs, enabling the design of systems to regulate therapeutic activity with greater precision. Our OligoPROTACs achieve proximitydependent degradation, which can be turned "off" by simply adding a third inhibitor DNA strand, through toehold-mediated strand displacement. As this control mechanism does not depend on the warheads used, it will serve as a general mechanism to control the activity of other PROTACs or any class of heterobifunctional molecules.