SMN2 Element 1 Antisense Compositions and Methods and Uses Thereof

摘要

The invention provides methods and compositions for treatment of spinal muscular atrophy (SMA). In one aspect of the invention, a series of compositions comprising an antisense oligonucleotide targeting the Element 1 site on the SMN2 pre-mRNA and a Morpholino backbone is disclosed. In another aspect of the invention, a method of treating SMA patients by modulating the splicing of SMN2 pre-mRNA to increase the amount of full-length SMN is disclosed. Certain embodiments of the inventive method comprise administering an E1-targeting antisense oligonucleotide, such as Morpholino based antisense oligonucleotide, to a SMA subject.

主权项

1. A composition for blocking the repressive activity of the Element 1 of the SMN2 pre-mRNA, the composition comprising an antisense oligonucleotide that comprises a sequence annealing to a first region and a second region of the SMN2 pre-mRNA, wherein the first region of the SMN2 pre-mRNA consists of the nucleotides between −134 to −90 relative to exon 7 of the SMN2 pre-mRNA and the second region of the SMN2 pre-mRNA consists of the nucleotides between −105 to −45 relative to exon 7 of the SMN2 pre-mRNA.