One aspect of the present invention relates to a double-stranded
oligonucleotide comprising at least one ligand. In certain embodiments, a
ligand is bound to only one of the two oligonucleotide strands comprising
the double-stranded oligonucleotide. In certain embodiments, both of the
oligonucleotide strands of the double-stranded oligonucleotide
independently comprise a bound ligand. In certain embodiments, the
oligonucleotide strands comprise at least one modified sugar moiety. In
certain embodiments, a phosphate linkage in one or both of the strands of
the oligonucleotide has been replaced with a phosphorothioate or
phosphorodithioate linkage. In a preferred embodiment, the ligand is
cholesterol or 5.beta.-cholanic acid. Another aspect of the present
invention relates to a single-stranded oligonucleotide comprising at
least one ligand. In certain embodiments, the oligonucleotide comprises
at least one modified sugar moiety. In certain embodiments, a phosphate
linkage of the oligonucleotide has been replaced with a phosphorothioate
or phosphorodithioate linkage. In a preferred embodiment, the ligand is
cholesterol or 5.beta.-cholanic acid. The ligand improves the
pharmacokinetic properties of the oligonucleotide.