Oligonucleoside methylphosphonates contain nonionic internucleotide bonds that resist degradation by cellular nucleases and allow the oligomers to be taken up intact by mammalian cells in culture. An-tisense methylphosphonate oligomers targeted against cellular or viral mRNA ini-tation codon or coding regions or against precursor mRNA splice sites effectively and specifically inhibit mRNA expression in cells. The efficacy of antisense methylphosphonate oligomers can be enhanced by derivatization with functional groups that allow the oligomer to covalently cross-link with its targeted mRNA. These oligonucleotide analogs will be useful tools for studying and controlling gene expression and are also promising candidates for development as therapeutic agents.
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