ANTISENSE OLIGONUCLEOTIDE INHIBITING ABERRANT SPLICING AND METHOD OF USING THE SAME

摘要

PROBLEM TO BE SOLVED: To provide a method of inhibiting aberrant splicing in a pre-mRNA molecule by using antisense oligonucleotides, to provide a method of upregulating gene expression, and to provide antisense oligonucleotide useful for performing the method.

SOLUTION: A method of inhibiting aberrant splicing in a pre-mRNA molecule containing a mutation is disclosed. When a mutation is present in the pre-mRNA, the mutation causes the pre-mRNA to be spliced incorrectly and produce an aberrant mRNA or mRNA fragment different from the mRNA ordinarily encoded by the pre-mRNA. The method comprises hybridizing an antisense oligonucleotide to the pre-mRNA molecule to create a duplex chain molecule under conditions which permit splicing. The antisense oligonucleotide is one which does not activate ribonuclease H, and is selected to block a member of the aberrant set of splice elements created by the mutation so that the normal intron is removed by splicing and the first mRNA molecule encoding a native protein is produced. Oligonucleotides useful for carrying out the method are also disclosed.

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