Antisense compounds

摘要

Provided herein are gapmer oligomeric compounds for reduction of target RNA in vivo comprising different nucleotide modifications within one or both wing regions. Also provided are methods of using such oligomeric compounds, including use in animals. In certain embodiments, such compound have desirable potency and toxicity characteristics.

主权项

1. A gapmer oligonucleotide consisting of 10 to 24 linked nucleosides wherein the gapmer oligonucleotide consists of three regions:
a gap region consisting of 6 to 10 linked deoxynucleosides; a 5′ wing region positioned at the 5′ end of the gap region and consisting of 1 to 7 linked nucleosides, wherein each nucleoside of the 5′ wing region comprises a modified sugar, and wherein at least one nucleoside of the 5′ wing region is a 2′-O(CH2)2OCH3 modified nucleoside; and a 3′ wing region positioned at the 3′ end of the gap region and consisting of 1 to 7 linked nucleosides, wherein each nucleoside of the 3′ wing region comprises a modified sugar, and wherein at least one nucleoside of the 3′ wing region is a 4′ to 2′ bicyclic nucleoside; and wherein a plurality of the internucleoside linkages of the gapmer oligonucleotide are phosphorothioate internucleoside linkages; or a pharmaceutically acceptable salt thereof.