TRICYCLO-DNA ANTISENSE OLIGONUCLEOTIDES, COMPOSITIONS, AND METHODS FOR THE TREATMENT OF DISEASE

摘要

PROBLEM TO BE SOLVED: To provide synthetic antisense oligonucleotides (AON) and methods employing AON for modifying splicing events that occur during pre-mRNA processing or for down-regulating the expression of mutated mRNA, for the treatment of diseases such as Duchenne Muscular Dystrophy.SOLUTION: A tricyclo-DNA antisense oligonucleotide (tc-DNA AON) for facilitating the skipping of an exon during processing of a dystrophin pre-mRNA, said tc-DNA AON containing between 10 and 18 tricyclo nucleotides, wherein 8-16 or 6-14 nucleotides of said tc-DNA AON are complementary to a dystrophin pre-mRNA intronic splice donor site, wherein 2-8 nucleotides of said tc-DNA AON are complementary to a dystrophin pre-mRNA exonic region, and wherein said intronic splice donor site is contiguous with 5' side of said exonic region.SELECTED DRAWING: None