Alpha-DNA.IX: Parallel annealing of alpha-anomeric oligodeoxyribonucleotides to natural mRNA is required for interference in RNase H mediated hydrolysis and reverse transcription

Abstract

ps- and aps-alpha anomeric oligodeoxyribonucleotides were designed to recognize in parallel (ps) or antiparallel (aps) orientation two different sites of a 1000 base-long mRNA. Northern blots experiments indicate that only ps-alpha-oligonucleotides were able to hybridize to the mRNA target. Furthermore, only ps-alpha-oligonucleotides were able, in a sequence specific way, to protect the mRNA target against RNase H mediated hydrolysis or to inactivate the priming capacity of beta-oligodeoxynucleotide probes in reverse transcription. Formation of parallel-stranded mRNA alpha-oligonucleotide miniduplexes which prevents hybridization of beta-oligonucleotide probes is the most likely mechanism accounting for these results. Use of alpha-oligonucleotides as potential gene control agents is discussed.