A nonconventional strategy in DNA nanodevice activation is determined by F. Ricci, J. Hong, and co-workers on page 5572, using a graphene and DNA based electro-responsive multilayer nanofilm by means of layer-by-layer assembly. The nanofilm onto a chip-electrode controls spontaneous conformational change of the DNA nanodevice via controlled release of complementary strands as a trigger, depending on electronic inputs including reductive potentials that allow efficient activation of a DNA nanodevice.