A wide range of molecular devices with nanoscale dimensions have been recently designed to perform a variety of functions in response to specific molecular inputs. Only limited examples, however, utilize antibodies as regulatory inputs. In response to this, here we report the rational design of a modular DNA-based nanomachine that can reversibly load and release a molecular cargo on binding to a specific antibody. We show here that, by using three different antigens (including one relevant to HIV), it is possible to design different DNA nanomachines regulated by their targeting antibody in a rapid, versatile and highly specific manner. The antibody-powered DNA nanomachines we have developed here may thus be useful in applications like controlled drug-release, point-of-care diagnostics and in vivo imaging.