Multimeric oligonucleotide compounds

A single-stranded nucleic acid compound comprising the general formula:

• 5′X3′-L-5′X3′,
• wherein each X is independently a single-stranded targeting oligonucleotide of 8 to 16 nucleotides in length having a region of complementarity comprising at least 7 contiguous nucleotides complementary to a target region of an mRNA, wherein adjacent nucleotides of the region of complementarity of each X comprise phosphorothioate linkages, and
• wherein L is a linker consisting of 1 to 10 pyrimidine nucleotides linked through phosphodiester linkages that links at least two Xs and that is i) more susceptible to cleavage in a liver mammalian extract than each X and ii) more susceptible to cleavage in liver mammalian extract than mammalian serum or plasma, and
• wherein when the target regions complementary to the first X and second X do not overlap in the mRNA, the 5′-end of the target region complementary to the first X and the 3′-end of the target region complementary to the second X are not within a distance of 0 to 4 nucleotides in the mRNA, and
• wherein at least one targeting oligonucleotide is a mixmer or gapmer.