Mixed-Backbone oligonucleotides as second-generation antisense agents with reduced phosphorothioate-related side effects

Mixed-backbone oligonucleotides containing alternative phosphorothioate and phosphodiester linkages in the 2′-O-methylribonucleosides segment show increased affinity with complementary targets, increased stability towards nucleases in vitro and in vivo, and reduced phosphorothioate-related prolongation of partial thromboplastin time compared to phosphorothioate oligodeoxynucleotides, thereby providing antisense agents with reduced side effects.