Oligonucleotides comprising one or more 4'-thioarabinonucleotides are described, as well as uses thereof for applications such as antisense- and RNAi-based gene silencing. 4'-thioarabinose-based phosphoramidite and H-phosphonate compounds are also described, as well as uses thereof for the synthesis of oligonucleotides comprising one or more 4'-thioarabinonucleotides.