BINDING-INDUCED DNA NANOMACHINES

摘要

The invention provides a binding-induced DNA nanomachine that can be activated by proteins and nucleic acids. This new type of nanomachine hamesses specific target binding to trigger assembly of separate DNA components that are otherwise unable to spontaneously assemble. Three-dimensional DNA tracks of high density are constructed on gold nanoparticles functionalized with hundreds of single-stranded oligonucleotides and tens of an affinity ligand. A DNA swing arm, free in solution, can be linked to a second affinity ligand. Binding of a target molecule to the two ligands brings the swing arm to AuNP and initiates autonomous, stepwise movement of the swing arm around the AuNP surface. The movement of the swing arm generates hundreds of oligonucleotides in response to a single binding event. The new nanomachines have several unique and advantageous features over DNA nanomachines that rely on DNA self-assembly.

主权项

1. A nanomachine comprising:
a nanoparticle; a first polynucleotide, the first polynucleotide having a first short sequence and a first spacer sequence, the first spacer sequence being conjugated to the nanoparticle and the first short sequence being conjugated to a first ligand; a second polynucleotide, having a first end and a second end, the first end being conjugated to the nanoparticle and the second end being conjugated to a second ligand; a third polynucleotide having a second short sequence, a second spacer sequence and a third ligand, the third ligand being conjugated to the second spacer sequence, the second short sequence being complementary to at least a portion of the first short sequence of the first polynucleotide; a fourth polynucleotide that is complimentary to at least a portion of the second short sequence and the second spacer sequence of the third polynucleotide and being bound to the third polynucleotide; and a target molecule that binds to the second ligand and the third ligand where, upon binding, the third polynucleotide is brought into proximity of the first polynucleotide such that the fourth polynucleotide is displaced and the first short sequence binds to the complimentary second short sequence, producing an enzymatic cleavage site, which is then cleaved by an enzyme and releasing the first ligand.