Antisense oligonucleotides which combat aberrant splicing and methods of using the same

A method of combatting aberrant splicing in a pre-mRNA molecule containing a mutation,

• wherein said pre-mRNA molecule contains a first set of splice elements defining a native intron which is removed by splicing when said mutation is absent to produce a first mRNA molecule encoding a native protein;
• and wherein said pre-mRNA further contains a second set of splice elements induced by said mutation and defining an aberrant intron different from said native intron, which aberrant intron is removed by splicing when said mutation is present to produce an aberrant second mRNA molecule different from said first mRNA molecule;
• said method comprising:
• hybridizing an antisense oligonucleotide to said pre-mRNA molecule to create a duplex molecule under conditions which permit splicing,
• wherein said antisense oligonucleotide does not activate RNase H;
• and wherein said oligonucleotide blocks a member of said aberrant second set of splice elements;
• so that said native intron is removed by splicing and said first mRNA molecule encoding a protein is produced.