Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures

WE have isolated a set of ligand-binding DNA sequences from a large pool of random sequence DNAs by selection and amplification in vitro, using similar methods to those described for the isolation of ligand-binding RNAs¹. The ligand-DNA inter-actions are both sequence- and ligand-specific, and are dependent on proper folding of the single-stranded DNA. Some ligands led to the isolation of more DNA sequences than RNA sequences, and vice versa. Analysis of individual sequences reveals that ligand binding is DNA-specific; RNAs of identical sequence could not interact with the same ligands. Ligand-binding DNAs might be more suitable than RNAs as potential pharmacological reagents^2-4 because of the greater stability of DNA. The apparent primacy of RNA in the early evolution of life^5-7 may have been due to its availability rather than to its functional superiority.