Abstract
Recent progress in the design of DNA oligonucleotides as ligands for binding specific sequences of DNA and RNA is described. Although DNA phosphodiester oligonucleotides have been reported to be unstable in biological media, new design strategies allow them to become stabilized considerably, thus possibly overcoming this limitation. A major new approach to increasing affinity and selectivity is the targeting of single-stranded nucleic acids by triplex formation. This involves the topological modification of linking two binding domains; one such strategy is to construct them in circular form. Cyclic DNA oligonucleotides can be designed to bind target DNA and RNA strands with much higher affinity and sequence selectivity than standard Watson-Crick complements. These recent advances in DNA oligonucleotide design may potentially lead to useful strategies for inhibition of specific disease-related genes.
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