UC Irvine

Background

Spinal Muscular Atrophy (SMA) is an autosomal recessive disease that leads to specific loss of motor neurons. It is caused by deletions or mutations of the survival of motor neuron 1 gene (SMN1). The remaining copy of the gene, SMN2, generates only low levels of the SMN protein due to a mutation in SMN2 exon 7 that leads to exon skipping.

To correct SMN2 splicing, we use Adenovirus type 5–derived vectors to express SMN2-antisense U7 snRNA oligonucleotides targeting the SMN intron 7/exon 8 junction. Infection of SMA type I–derived patient fibroblasts with these vectors resulted in increased levels of exon 7 inclusion, upregulating the expression of SMN to similar levels as in non–SMA control cells.

These results show that Adenovirus type 5–derived vectors delivering U7 antisense oligonucleotides can efficiently restore full-length SMN protein and suggest that the viral vector-mediated oligonucleotide application may be a suitable therapeutic approach to counteract SMA.