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- Title
Restoration of Full-Length SMN Promoted by Adenoviral Vectors Expressing RNA Antisense Oligonucleotides Embedded in U7 snRNAs.
- Authors
Geib, Till; Hertel, Klemens J.
- Abstract
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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.
- Subjects
SPINAL muscular atrophy; ADENOVIRUS diseases; ANTISENSE RNA; OLIGONUCLEOTIDES; PROTEINS; FIBROBLASTS; EXONS (Genetics); MOTOR neurons; CELLS
- Publication
PLoS ONE, 2009, Vol 4, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0008204