One aspect of the present invention relates to a double-strandedoligonucleotide comprising at least one ligand. In certain embodiments, aligand is bound to only one of the two oligonucleotide strands comprising thedouble-stranded oligonucleotide. In certain embodiments, both of theoligonucleotide strands of the double-stranded oligonucleotide independentlycomprise a bound ligand. In certain embodiments, the oligonucleotide strandscomprise at least one modified sugar moiety. In certain embodiments, aphosphate linkage in one or both of the strands of the oligonucleotide hasbeen replaced with a phosphorothioate or phosphorodithioate linkage. In apreferred embodiment, the ligand is cholesterol or 5.beta.-cholanic acid.Another aspect of the present invention relates to a single-strandedoligonucleotide comprising at least one ligand. In certain embodiments, theoligonucleotide comprises at least one modified sugar moiety. In certainembodiments, a phosphate linkage of the oligonucleotide has been replaced witha phosphorothioate or phosphorodithioate linkage. In a preferred embodiment,the ligand is cholesterol or 5.beta.-cholanic acid. The ligand improves thepharmacokinetic properties of the oligonucleotide.
