Nanopores Analyze RNA-Drug Complexes

Synthetic nanopores can rapidly analyze individual RNA-drug complexes, scientists report (ACS Nano, DOI: 10.1021/nn203764j). Most drug-binding assays for RNA depend on fluorescent labels or surface immobilization. Meni Wanunu of Northeastern University; Aleksei Aksimentiev of the University of Illinois, Urbana-Champaign; Marija Drndic of the University of Pennsylvania; and coworkers use 3-nm nanopores fabricated in an ultrathin silicon nitride membrane to perform label-free, rapid, and sensitive assays for RNA molecules bound to antibacterial drugs. As individual RNA molecules pass through a nanopore, they produce an electrical signal that is measured with two electrodes. RNA complexes can be distinguished from unbound RNA by the resulting electrical signatures. The researchers show that the electronic signature of prokaryotic ribosomal A-site RNA varies depending on whether a small-molecule drug is bound to it. By titrating the drug with RNA and counting the bound fraction, the researchers calculate binding affinities that agree with those determined by other methods. The experiments take only seconds to perform, so RNA binding kinetics can potentially be probed with these sensitive molecular counters, the researchers note.