PROGRESS IN DEVELOPMENTS OF TRIPLEX-BASED STRATEGIES

Recognition of B-DNA by oligonucleotides that form triple helices is a unique method to specifically recognize sequences of double-stranded DNA, Recently, some significant limitations of the triple-based applic ations have been overcome. Stable intermolecular triplexes can be form ed under physiologic conditions, Binding affinities of modified oligon ucleotides to their target sequence due to Hoogsteen or reverse Hoogst een hydrogen bonding interactions are now in the range of those obtain ed for duplex formation via Watson-Crick hydrogen bonding interactions even if the kinetics may be quite different. Progress has been made t oward developing general procedures to determine the molecular mechani sms of action of tripler-forming oligonucleotides (TFO) administered t o cultured cells to provide a rational proof-of-concept for antigene s trategies, The antigene strategy has reached a point where TFOs can be used to interfere with several biologic processes (replication, trans cription, recombination, repair) in relevant systems both in vitro and ex vivo.