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