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.L'invention concerne des oligonucléotides antisens comprenant au moins une liaison phosphorodiamidate N3'→P5' (NPN) dans le squelette, ainsi que des méthodes d'utilisation associées. Les oligonucléotides antisens peuvent prévenir ou diminuer efficacement l'expression protéique.