In Vitro Selection of Functional Nucleic Acids

David S. Wilson, Jack W. Szostak

doi:10.1146/annurev.biochem.68.1.611

<jats:p>▪ Abstract In vitro selection allows rare functional RNA or DNA molecules to be isolated from pools of over 10<jats:sup>15</jats:sup>different sequences. This approach has been used to identify RNA and DNA ligands for numerous small molecules, and recent three-dimensional structure solutions have revealed the basis for ligand recognition in several cases. By selecting high-affinity and -specificity nucleic acid ligands for proteins, promising new therapeutic and diagnostic reagents have been identified. Selection experiments have also been carried out to identify ribozymes that catalyze a variety of chemical transformations, including RNA cleavage, ligation, and synthesis, as well as alkylation and acyl-transfer reactions and N-glycosidic and peptide bond formation. The existence of such RNA enzymes supports the notion that ribozymes could have directed a primitive metabolism before the evolution of protein synthesis. New in vitro protein selection techniques should allow for a direct comparison of the frequency of ligand binding and catalytic structures in pools of random sequence polynucleotides versus polypeptides.</jats:p>

In Vitro Selection of Functional Nucleic Acids

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