Oligonucleotide therapy for Wilson disease

An antisense oligonucleotide comprising 10 to 50 nucleotides with a nucleobase sequence at least 95% complementary over the entire length of the oligonucleotide to an ATPase copper transporting beta protein (ATP7B) pre-mRNA target sequence in exon 6, a 5′-flanking intron, a 3′-flanking intron, or a combination of exon 6 and the 5′-flanking or 3′-flanking intron;

• wherein the antisense oligonucleotide comprises at least one modified nucleobase, at least one modified internucleoside linkage, or at least one modified sugar nucleoside, or wherein the antisense oligonucleotide is a morpholino oligomer;
• and
• a) the ATP7B target sequence:
• (i) comprises at least one nucleotide located among positions 54672-54680 or 54691-54701 in SEQ ID NO:
• 1, wherein the 5′-terminal nucleotide of the oligonucleotide is complementary to neither position 54695 nor position 54696 of SEQ ID NO:
• 1;
• (ii) is located within the 5′-flanking intron among positions up to 54517 in SEQ ID NO:
• 1, the 5′-flanking intron among positions 54522 to 54581 in SEQ ID NO:
• 1 or the combination of the 5′-flanking intron and exon 6 among positions 54562 to 54593 in SEQ ID NO:
• 1;
• or
• (iii) is located among positions 54631 to 54677 or 54655 to 54738 in SEQ ID NO:
• 1 or
• b) the nucleobase sequence has at least 95% sequence identity to SEQ ID NO:
• 3, 4, 5, 6, 7, 8, 9, 10, 11, 22, 23, 24, 25, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154 or 155.