Compounds and methods useful for modulating gene splicing

A method for selecting a first mRNA transcript in a gene comprising at least two mRNA transcripts, the method comprising administering an antisense oligonucleotide comprising 14 to 30 linked nucleotides having at least 12 contiguous nucleobases complementary to an equal length portion of a target pre-mRNA;

• wherein the antisense oligonucleotide targets a splice site of the pre-mRNA for a second mRNA transcript thereby blocking the splice site for the second mRNA transcript and directing splicing of the pre-mRNA to the first mRNA transcript;
• and wherein the antisense oligonucleotide comprises 1 to 3 regions each region independently comprising from 2 to 5 consecutive deoxyribonucleotides and the remaining nucleotides are 2′-substituted, non-ionic or constrained sugar nucleotides or combinations thereof.

A method of treating a disease or disorder in a subject wherein modulating RNA processing would be beneficial to treat the subject, the method comprising administering an antisense oligonucleotide comprising 14 to 30 linked nucleotides having at least 12 contiguous nucleobases complementary to an equal length portion of a target RNA, wherein the antisense oligonucleotide comprises 1 to 3 regions each region independently comprising from 2 to 5 consecutive deoxyribonucleotides and the remaining nucleotides are 2′-substituted, non-ionic or constrained sugar nucleotides, or combinations thereof.

A method of inducing nonsense mediated decay of a target RNA comprising administering an antisense oligonucleotide comprising 14 to 30 linked nucleotides having at least 12 contiguous nucleobases complementary to an equal length portion of a target RNA, wherein the antisense oligonucleotide comprises 1 to 3 regions each region independently comprising from 2 to 5 consecutive deoxyribonucleotides and the remaining nucleotides are 2′-substituted, non-ionic or constrained sugar nucleotides, or combinations thereof.

A method of increasing a level of mRNA encoding a protein or a functional mRNA and increasing expression of the protein or the functional mRNA comprising administering an antisense oligonucleotide comprising 14 to 30 linked nucleotides having at least 12 contiguous nucleobases complementary to an equal length portion of a target RNA, wherein the antisense oligonucleotide comprises 1 to 3 regions each region independently comprising from 2 to 5 consecutive deoxyribonucleotides and the remaining nucleotides are 2′-substituted, non-ionic or constrained sugar nucleotides, or combinations thereof.

An antisense oligonucleotide comprising 14 to 30 linked nucleotides having at least 12 contiguous nucleobases complementary to an equal length portion of a target pre-mRNA comprising a retained intron, wherein the antisense oligonucleotide comprises 1 to 3 regions each region independently comprising from 2 to 5 consecutive deoxyribonucleotides and the remaining nucleotides are 2′-substituted, non-ionic or constrained sugar nucleotides, or combinations thereof.