Affiliation:
1. Departments of Neurology, Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA.
2. Departments of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA.
Abstract
Resisting Repeats
A set of diseases, including myotonic dystrophy, are caused by the expansion of a simple repeat in genomic DNA, which, when transcribed into RNA, can be toxic to other cellular processes. Ameliorating the effects of this toxic, repeat-laden RNA may also relieve the symptoms of the disease.
Wheeler
et al.
(p.
336
; see the Perspective by
Cooper
) developed an antisense morpholino oligonucleotide complementary to the expanded repeats found in the myotonic dystrophy protein kinase messenger RNA (mRNA). The morpholino bound the repeats in vitro and displaced the inappropriately bound and sequestered RNA splicing factor, Muscleblind-like 1. In an in vivo mouse model for myotonic dystrophy, local injection of the morpholino corrected a number of cellular defects in muscle, including the alternative mRNA splicing of several genes, among them the muscle-specific chloride channel, CIC1, leading to a marked reduction in the myotonia.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
337 articles.
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