摘要 |
One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non - natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, th e ligand is a steroid or aromatic compound. In certain embodiments, only one o f the two oligonucleotide strands comprising the double-stranded oligonucleoti de contains a ligand tethered to an altered or non-natural nucleobase. In certa in embodiments, both of the oligonucleotide strands comprising the double- stranded oligonucleotide independently contain a ligand tethered to an alter ed or non-natural nucleobase. In certain embodiments, the oligonucleotide stran ds comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least o ne ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, the robose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least on e phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage. |