The present disclosure relates to RNA amidates and thioamidates useful for
RNA interference applications. The RNA amidates and thioamidates contain
at least one internucleoside linkage chosen from ribo-N3'.fwdarw.P5'
phosphoramidate (NP) and ribo-N3'.fwdarw.P5' thiophosphoramidate (NPS)
linkages, and optionally further containing at least one covalently
conjugated lipid moiety. Compositions comprising the amidates and
thioamidates are disclosed, as are methods for their use in modulating
gene expression.