Evolution and protein packaging of small-molecule RNA aptamers.

Jolene L Lau, Michael M Baksh, Jason D Fiedler, Steven D Brown, Amanda Kussrow, Darryl J Bornhop, Phillip Ordoukhanian, M G Finn

Index: ACS Nano 5(10) , 7722-7729, (2011)

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Abstract

A high-affinity RNA aptamer (K(d) = 50 nM) was efficiently identified by SELEX against a heteroaryldihydropyrimidine structure, chosen as a representative drug-like molecule with no cross reactivity with mammalian or bacterial cells. This aptamer, its weaker-binding variants, and a known aptamer against theophylline were each embedded in a longer RNA sequence that was encapsidated inside a virus-like particle by a convenient expression technique. These nucleoprotein particles were shown by backscattering interferometry to bind to the small-molecule ligands with affinities similar to those of the free (nonencapsidated) aptamers. The system therefore comprises a general approach to the production and sequestration of functional RNA molecules, characterized by a convenient label-free analytical technique.