This invention relates to antisense oligonucleotides comprising at least one N3′→P5′ phosphorodiamidate linkage (NPN) in the backbone, and kits and pharmaceutical compositions thereof, useful for modulating gene expression involved in the pathogenesis of a disease. Also included are compounds useful as building blocks of said antisense oligonucleotides and methods of preparing said antisense oligonucleotides and building block compounds including NPN linkages.