ANTISENSE OLIGOMER COMPOUNDS
A modified antisense oligonucleotide of about 10 to about 40 nucleobases is disclosed. The oligonucleotide comprises a targeting sequence having a region complementary to at least one string of three or more identical contiguous nucleobases in a target sequence, wherein the target sequence comprises at least one additional nucleobase compared to the region of the targeting sequence and the at least one additional nucleobase has no complementary nucleobase in the region of the targeting sequence, and wherein the targeting region complementary to the at least one string of three or more identical contiguous nucleobases is internal to the targeting sequence.
1 . A modified antisense oligonucleotide of about 10 to about 40 nucleobases comprising: a targeting sequence having a region complementary to at least one string of three or more identical contiguous nucleobases in a target sequence, wherein the target sequence comprises at least one additional nucleobase compared to the region of the targeting sequence and the at least one additional nucleobase has no complementary nucleobase in the region of the targeting sequence, and wherein the targeting region complementary to the at least one string of three or more identical contiguous nucleobases is internal to the targeting sequence.
2 . The modified antisense oligonucleotide of claim 1 , wherein the targeting sequence comprises at least one string of three nucleobases.
3 . The modified antisense oligonucleotide of claim 1 , wherein the targeting sequence comprises at least one string of four nucleobases.
4 . The modified antisense oligonucleotide of claim 1 , wherein the at least one string of three or more nucleobases comprises at least one string of three or more guanine bases.
5 . The modified antisense oligonucleotide of claim 1 , wherein the modified antisense oligonucleotide is conjugated to a peptide.
6 . The modified antisense oligonucleotide of claim 1 , wherein the target sequence comprises an exon target associated with Duchenne muscular dystrophy.
7 . The modified antisense oligonucleotide of claim 6 , wherein the target sequence comprises exon 44 in the processing of human dystrophin pre-processed mRNA.
8 . The modified antisense oligonucleotide of claim 6 , wherein the targeting sequence comprises any one of SEQ ID NOs: 2-7.
9 . The modified antisense oligonucleotide of claim 6 , wherein the target sequence comprises exon 45, 51, or 53 in the processing of human dystrophin pre-processed mRNA.
10 . The modified antisense oligonucleotide of claim 9 , wherein the targeting sequence comprises any one of SEQ ID NOs: 72-120.
11 . The modified antisense oligonucleotide of claim 1 , wherein the target sequence comprises an exon target associated with spinal muscular atrophy.
12 . The modified antisense oligonucleotide of claim 11 , wherein the target sequence comprises a region adjacent to exon 7 in the processing of human SMN2 pre-processed mRNA.
13 . The modified antisense oligonucleotide of claim 11 , wherein the targeting sequence comprises any one of SEQ ID NOs: 9-25.
14 . The modified antisense oligonucleotide of claim 1 , wherein the target sequence comprises an exon target associated with glycogen storage disease type II.
15 . The modified antisense oligonucleotide of claim 14 , wherein the target sequence comprises a region associated with exon 2 of the human acid alpha-glucosidase pre-processed mRNA.
16 . The modified antisense oligonucleotide of claim 14 , wherein the targeting sequence comprises any one of SEQ ID NOs: 26-68.
17 . A modified antisense oligonucleotide of about 10 to about 40 nucleobases comprising a deletion sequence wherein the deletion sequence comprises at least one base sequence according to SEQ ID NOs: 1-128, wherein at least one nucleobase from the base sequence has been deleted, and wherein the at least one nucleobase that has been deleted is internal to the base sequence.
18 . The modified antisense oligonucleotide of claim 17 , wherein the base sequence is SEQ ID NO: 69, SEQ ID NO: 70, or SEQ ID NO: 71.