Abstract
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.
Highlights
In nucleic acid nanotechnology synthetic nucleic acids are used as self-assembling bricks to build nanoscale devices or structural motifs of increasing complexity[9,10,11]
Our strategy to rationally regulate DNA nanostructures formation with antibodies starts from the consideration that the isothermal assembly and disassembly of such nanostructures can be induced by regulator strands that can be released by designed DNAbased circuits[17,29]
Antibody binding to the two antigen-conjugated split input strands induces their co-localization triggering stem formation and the reconstitution of a functional DNA input complex that can lead to strand displacement activation (Fig. 1a)
Summary
In nucleic acid nanotechnology synthetic nucleic acids are used as self-assembling bricks to build nanoscale devices or structural motifs of increasing complexity[9,10,11]. With regards to DNA structural motifs, the control of the spatial geometry of DNAbased shapes using genetically-encoded proteins[24] and the use of proteins, peptides and lipid bilayers as building blocks or supportive scaffolds to build DNA chimera nanostructures has been demonstrated[25,26,27,28]. While these examples clearly demonstrate the versatility of DNA-based nanostructures selfassembly process, the possibility to control the assembly or disassembly of such structures with specific relevant biomolecular markers such as antibodies has not yet been demonstrated. Motivated by the above arguments, here we demonstrate the orthogonal regulation of DNA-based circuits with specific antibodies that allow isothermal dynamic control of self-assembly and disassembly of DNA structures
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