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PLoS One. 2014 Apr 23;9(4):e95362. doi: 10.1371/journal.pone.0095362. eCollection 2014.

RNA interference-based therapy for spinocerebellar ataxia type 7 retinal degeneration.

Author information

1
Interdisciplinary program in Genetics, University of Iowa, Iowa City, Iowa, United States of America.
2
Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of America.
3
Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
4
Departments of Pediatrics, Cellular & Molecular Medicine, and Neurosciences, Division of Biological Sciences, the Institute for Genomic Medicine, and the Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California, United States of America.
5
Interdisciplinary program in Genetics, University of Iowa, Iowa City, Iowa, United States of America; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America; Department of Neurology, University of Iowa, Iowa City, Iowa, United States of America; Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States of America.

Abstract

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disease characterized by loss of motor coordination and retinal degeneration with no current therapies in the clinic. The causative mutation is an expanded CAG repeat in the ataxin-7 gene whose mutant protein product causes cerebellar and brainstem degeneration and retinal cone-rod dystrophy. Here, we reduced the expression of both mutant and wildtype ataxin-7 in the SCA7 mouse retina by RNA interference and evaluated retinal function 23 weeks post injection. We observed a preservation of normal retinal function and no adverse toxicity with ≥50% reduction of mutant and wildtype ataxin-7 alleles. These studies address an important safety concern regarding non-allele specific silencing of ataxin-7 for SCA7 retinal therapy.

PMID:
24759684
PMCID:
PMC3997397
DOI:
10.1371/journal.pone.0095362
[Indexed for MEDLINE]
Free PMC Article

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