Spinal Muscular Atrophy (SMA) treatment via targeting of SMN2 splice site inhibitory sequences
    2.
    发明申请
    Spinal Muscular Atrophy (SMA) treatment via targeting of SMN2 splice site inhibitory sequences 有权
    通过靶向SMN2剪接位点抑制性序列的脊髓肌萎缩(SMA)治疗

    公开(公告)号:US20070292408A1

    公开(公告)日:2007-12-20

    申请号:US11295725

    申请日:2005-12-05

    Abstract: The present invention is directed to methods and compositions capable of blocking the inhibitory effect of a newly-identified intronic inhibitory sequence element, named ISS-N1 (for “intronic splicing silencer”), located in the SMN2 gene. The compositions and methods of the instant invention include oligonucleotide reagents (e.g., oligoribonucleotides) that effectively target the SMN2 ISS-N1 site in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The ISS-N1 blocking agents of the invention cause elevated expression of SMN protein, thus compensating for the loss of SMN protein expression commonly observed in subjects with spinal muscular atrophy (SMA).

    Abstract translation: 本发明涉及能够阻断位于SMN2基因中的新鉴定的内含子抑制性序列元件(称为ISS-N1(对于“内含子剪接沉默子”)的抑制作用的方法和组合物。 本发明的组合物和方法包括有效靶向SMN2前mRNA中的SMN2 ISS-N1位点的寡核苷酸试剂(例如寡核糖核苷酸),由此调节SMN2前mRNA的剪接以将其包括在加工转录物中的外显子7。 本发明的ISS-N1阻断剂引起SMN蛋白的升高的表达,从而补偿在脊髓性肌萎缩(SMA)受试者中通常观察到的SMN蛋白表达的丧失。

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