Circular Oligonucleotides: New Concepts in Oligonucleotide Design

Recent progress in the synthesis and properties of circular oligonucleotides as ligands for DNA and RNA and as templates for polymerase enzymes is described. Small synthetic circular DNAs, RNAs, and chimeric analogues ranging from 28 to 74 nucleotides in size have been synthesized with the use of a nonenzymatic ligation strategy. Some of these were designed to undergo triplex formation with single-stranded DNA and RNA targets, and many bind with affinities and sequence selectivities considerably greater than those seen for linear oligonucleotides. Design strategies and modes of binding are discussed in the light of possible use of such molecules as hybridization probes, molecular diagnostics, and sequence-specific inhibitors of gene expression. Small circular oligonucleotides have also been shown to act as unusually efficient templates for DNA and RNA polymerases, which produce long, repeating copies of the circular sequence by a rolling circle process.