Antisense oligonucleotides which combat aberrant splicing and me

Details Antisense oligonucleotides which combat aberrant splicing and me Antisense oligonucleotides which combat aberrant splicing and me

1999-04-30

1999-11-02

LeGuyader, John L.

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

Method of regulating cell metabolism or physiology

435 6, 435 911, 435325, 536 231, 536 243, 536 2431, 536 2433, 536 245, C12Q 168, C12N 1585, C02H 2104

Patent

active

059768797

ABSTRACT:
A method of combatting aberrant splicing in a pre-mRNA molecule containing a mutation is disclosed. When present in the pre-mRNA, the mutation causes the pre-mRNA to splice 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 molecule under conditions which permit splicing. The antisense oligonucleotide is one which does not activate RNase H, and is selected to block a member of the aberrant set of splice elements created by the mutation so that the native 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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