Spinal muscular atrophy treatment via targeting smn2 catalytic core

Spinal muscular atrophy treatment via targeting smn2 catalytic core" (2014). Iowa State University Patents. Paper 317. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 82 days. See application ?le for complete search history. An antisense microwalk reveals critical role of an intronic position linked to a unique long-distance interaction in pre-mRNA splicing " , RNA (2010), pp. 1-15. (57) ABSTRACT The present invention is directed to methods and composi tions for blocking the effect of the intronic inhibitory splicing region of intron 7 of the SMN2 gene. The compositions and methods of the instant invention include short oligonucle otide reagents (e.g., oligoribonucleotides) that effectively tar get sites in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the pro cessed transcript. The short target regions are 8-mers and 5-mers and also include the identi?cation of a single nucle otide base that is essential for initiating a long distance stearic inhibitory interactions as well as novel targets distant from intron 7 which block the intronic inhibitory splicing of the same. These short target regions and concomitant inhibitory blocking oligonucleotides are less expensive and easier to manufacture and are small enough to cross the blood brain barrier.