This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (1)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Neuromuscular diseases  • Drug Therapy  • Drug Therapy, Other  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Exon Skipping Breaks New Ground

Toshifumi Yokota, PhD; Shin’ichi Takeda, MD, PhD; Qi-Long Lu, MD, PhD; Terence A. Partridge, PhD; Akinori Nakamura, MD, PhD; Eric P. Hoffman, PhD

Arch Neurol. 2009;66(1):32-38.

Antisense oligonucleotides are short nucleic acid sequences designed for use as small-molecule drugs. They recognize and bind to specific messenger RNA (mRNA) or pre-mRNA sequences to create small double-stranded regions of the target mRNA that alter mRNA splicing patterns or inhibit protein translation. Antisense approaches have been actively pursued as a form of molecular medicine for more than 20 years, but only one has been translated to a marketed drug (intraocular human immunodeficiency virus treatment). Two recent advances foreshadow a change in clinical applications of antisense strategies. First is the development of synthetic DNA analogues that show outstanding stability and sequence specificity yet little or no binding to modulator proteins. Second is the publication of impressive preclinical and clinical data using antisense in an exon-skipping strategy to increase dystrophin production in Duchenne muscular dystrophy. As long-standing barriers are successfully circumvented, attention turns toward scale-up of production, long-term toxicity studies, and the challenges to traditional drug regulatory attitudes presented by tightly targeted sequence-specific drugs.

Author Affiliations: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC (Drs Yokota, Partridge, and Hoffman); Department of Molecular Medicine, National Institutes for Neuroscience, Tokyo, Japan (Drs Takeda and Nakamura); and McColl-Lockwood Laboratory for Muscular Dystrophy Research, Neuromuscular/ALS Center, Carolinas Medical Center, Charlotte, North Carolina (Dr Lu).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

This Month in Archives of Neurology
Arch Neurol. 2009;66(1):17-18.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

More Than Baby Steps: Perspectives on Pediatric Translational Research
Connor et al.
Sci Transl Med 2009;1:2cm2-2cm2.
FULL TEXT