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Therapeutic Modulation of DMD Splicing by Blocking Exonic Splicing Enhancer Sites with Antisense Oligonucleotides
Author(s) -
AARTSMARUS A.,
JANSON A.A.M.,
HEEMSKERK J.A.,
DE WINTER C.L.,
VAN OMMEN G.J.B.,
VAN DEUTEKOM J.C.T.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1348.058
Subject(s) - exon skipping , exon , rna splicing , exonic splicing enhancer , enhancer , oligonucleotide , chemistry , alternative splicing , computational biology , microbiology and biotechnology , biology , genetics , gene , gene expression , rna
Antisense oligonucleotides (AONs) can be used to correct the disrupted reading frame of Duchenne muscular dystophy patients (DMD). We have a collection of 121 AONs, of which 79 are effective in inducing the specific skipping of 38 out of the 79 different DMD exons. All AONs are located within exons and were hypothesized to act by steric hindrance of serine‐arginine rich (SR) protein binding to exonic splicing enhancer (ESE) sites. Indeed, retrospective in silico analysis of effective versus ineffective AONs revealed that the efficacy of AONs is correlated to the presence of putative ESE sites (as predicted by the ESEfinder and RESCUE‐ESE software). ESE predicting software programs are thus valuable tools for the optimization of exon‐internal antisense target sequences.