The molecular recognition and self-assembly capabilities of nucleic acids are a key driving force behind nearly all of the chemical processes that make life possible.  The ability of nucleic acids to selectively recognize other nucleic acids, as well as small molecules and proteins, has been refined by billions of years of evolution.  Realizing the tremendous potential of these exquisite recognition and assembly capabilities, researchers have harnessed these properties in the laboratory with the goal of redirecting DNA and RNA to perform tasks outside of their canonical biological roles.One example of this is the development of DNA split aptamers, which are comprised of two nucleic acid strands that only assemble in the presence of a specific small-molecule or protein target.  We have explored the use of split aptamers as a recognition element to transduce the presence of a small-molecule into the output of DNA ligation.  Reactive groups are appended to the termini of the split aptamer fragments. If the target small molecule is present, it directs assembly of the aptamer, bringing the reactive groups into close proximity and thus promoting ligation of the DNA strands.  This ligation event can be detected using an enzyme-linked output or in the format of a lateral flow sensor.  Additionally, we have demonstrated that the increased effective molarity provided by DNA assembly is sufficient to enable the use of non-bioorthogonal chemistry in complex biological fluids.

Small-molecule detection using DNA assembly-driven reactions

246th National Meeting (2013)

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