N. Delihas et al., NATURAL ANTISENSE RNA TARGET RNA INTERACTIONS - POSSIBLE MODELS FOR ANTISENSE OLIGONUCLEOTIDE DRUG DESIGN, Nature biotechnology, 15(8), 1997, pp. 751-753
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.