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.

Here we report a rational strategy to orthogonally control assembly and disassembly of DNA-based nanostructures using specific IgG antibodies as molecular inputs. We first demonstrate that the binding of a specific antibody to a pair of antigen-conjugated split DNA input-strands induces their co-localization and reconstitution into a functional unit that is able to initiate a toehold strand displacement reaction. The effect is rapid and specific and can be extended to different antibodies with the expedient of changing the recognition elements attached to the two split DNA input-strands. Such an antibody-regulated DNA-based circuit has then been employed to control the assembly and disassembly of DNA tubular structures using specific antibodies as inputs. For example, we demonstrate that we can induce self-assembly and disassembly of two distinct DNA tubular structures by using DNA circuits controlled by two different IgG antibodies (anti-Dig and anti-DNP antibodies) in the same solution in an orthogonal way.

Here we demonstrate a versatile platform for the one-step fluorescent detection of both monovalent and multivalent proteins. Specifically, we have designed a conformational-switching, stem-loop DNA scaffold that presents a small molecule, polypeptide or nucleic-acid (e.g., aptamer, transcription factor binding site) recognition element on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair. The sensors are rapid (<10 minutes) and selective, supporting the ready detection of specific proteins even in complex samples, such as blood serum. The platform is also versatile: using it we have measured five bivalent proteins (four antibodies and the chemokine platelet-derived growth factor) and two monovalent proteins (a Fab fragment and the transcription factor TBP) all with low nanomolar detection limits and no detectable cross-reactivity.

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Here we demonstrate that we can rationally and finely control the functionality of different DNA-based nanodevices and nanoswitches using electronic inputs.