Patent ID: 9732341
Date: 2017-08-15
CPC Classifications: A61P,C12N

Claim:
1. A method of delivering multiple single stranded targeting oligonucleotides to a liver or kidney cell, the method comprising: contacting a liver or kidney cell with a compound under conditions in which the compound enters into the cell, wherein the compound comprises the general formula: X-L-[X-L] wherein i is an integer from 0 to 9, the value of which indicates the number of units of [X-L] 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 a genomic target sequence, wherein adjacent nucleotides of the region of complementarity of each X comprise phosphorothioate linkages, and each L is an single stranded oligonucleotide linker consisting of 2 to 4 contiguous thymidine or uridine nucleotide residues linked through phosphodiester linkages, that links at least two Xs and that is more susceptible to cleavage in a mammalian liver or kidney cell extract than each X, wherein when i=0, and the general formula is 5′X3′-L-5′X3′ and when the target regions complementary to the first X and second X do not overlap in the genomic target sequence, 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 genomic target sequence, wherein at least one L does not comprise an oligonucleotide having a self-complementary nucleotide sequence, and wherein at least one L does not comprise an oligonucleotide having a nucleotide sequence that is complementary to a region of the genomic target sequence that is contiguous with the target regions complementary to two immediately flanking Xs.