NATURAL ANTISENSE RNA TARGET RNA INTERACTIONS - POSSIBLE MODELS FOR ANTISENSE OLIGONUCLEOTIDE DRUG DESIGN

Current antisense oligonucleotides designed for drug therapy rely on W atson-Crick base pairing for the specificity of interactions between a ntisense and target molecules. However, thermodynamically stable duple xes containing non-Watson-Crick pairs have been formed with synthetic oligonucleotides. There are also numerous examples of non-canonical ba se pairs that participate in stable intra- and intermolecular RNA/RNA pairing in prokaryotic and eukaryotic cells, Several natural antisense RNA/target RNA duplexes contain looped-out and bulged positions as we ll as non-canonical pairs as exemplified by formation of the Escherich ia coli antisense micF RNA/ompF mRNA duplex, Secondary structures and the phylogenetic conservation of nucleotide sequences are well charact erized in this system, Natural antisense/target interactions may serve as models for determining possible and optimal antisense/target inter actions in oligonucleotide drug design.