Abstract: The present disclosure provides antisense oligonucleotides, compositions, and methods that target ATP7B exon 6 or a flanking intron, thereby modulating splicing of ATP7B pre-mRNA to increase the level of ATP7B mRNA molecules having exon 6, e.g., to provide a therapy for Wilson disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to an ATP7B 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.

Abstract: The present disclosure provides antisense oligonucleotides, compositions, and methods that target a ABCA4 exon or intron flanking an exon, thereby modulating splicing of ABCA4 pre-mRNA to increase the level of wild type ABCA4 mRNA molecules, e.g., to provide a therapy for retinitis pigmentosa, cone-rod dystrophy, or Stargardt disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to a ABCA4 pre-mRNA target sequence in an intron, 5?-flanking intron, a 3?-flanking intron, or a combination of an exon and the 5?-flanking or 3?-flanking intron.

Abstract: The present disclosure provides compositions and methods for treating a disorder associated with mutations in the CEP290 gene. The disclosure includes synthetic polynucleotides for skipping a reading-frame of a CEP290 pre-RNA, yielding a CEP290 translated product that lacks one or more exons. The disclosure also provides methods of treating patients with the synthetic polynucleotides disclosed herein.

Abstract: The present disclosure provides antisense oligonucleotides, compositions, and methods that target a LIPA intron flanking exon 8, thereby modulating splicing of LIPA pre-mRNA to increase the level of LIPA mRNA molecules having exon 8, e.g., to provide a therapy for Wolman Disease or Cholesteryl Ester Storage Disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to a LIPA pre-mRNA target sequence in a 5?-flanking intron, a 3?-flanking intron, or a combination of exon 8 and the 5?-flanking or 3?-flanking intron.

Abstract: The present disclosure provides antisense oligonucleotides, compositions, and methods that target ATP7B exon 6 or a flanking intron, thereby modulating splicing of ATP7B pre-mRNA to increase the level of ATP7B mRNA molecules having exon 6, e.g., to provide a therapy for Wilson disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to an ATP7B 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.

Abstract: The present disclosure provides compositions and methods for treating a disorder associated with mutations in the CEP290 gene. The disclosure includes synthetic polynucleotides for skipping a reading-frame of a CEP290 pre-RNA, yielding a CEP290 translated product that lacks one or more exons. The disclosure also provides methods of treating patients with the synthetic polynucleotides disclosed herein.