ANTISENSE OLIGONUCLEOTIDES FOR MODULATING SURVIVAL MOTOR NEURON 2 (SMN2) SPLICING

摘要

AbstractAntisense oligonucleotides for modulating SMN2 splicingThe invention provides an isolated antisense fusion oligonucleotide comprising a first oligonucleotide sequence joined to a second oligonucleotide sequence,5 wherein the second oligonucleotide sequence comprises a sequence complementary to a first splicing regulatory element (SRE) in SMN precursor mRNA and the first oligonucleotide sequence comprises a sequence complementary to a sequence of the SMN precursor mRNA other than the said first SRE complementary to the second oligonucleotide sequence. The10 antisense fusion oligonucleotide is for modulating splicing of SMN2 mRNA. In particular, the antisense fusion oligonucleotide enhances exon 7 inclusion in SMN2 mRNA and may be used in spinal muscular atrophy therapy.Fig. 7