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.
Zhou
W
W
Hybridon Inc., Milford, MA 01757, USA.
Agrawal
S
S
D004355:Drug Stability; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000494:pharmacology*; D010314:Partial Thromboplastin Time; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000009:adverse effects*
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides