Potent and Selective Antisense Oligonucleotides Targeting Single-Nucleotide Polymorphisms in the Huntington Disease Gene / Allele-Specific Silencing of Mutant Huntingtin

• Published in: Molecular therapy Vol. 19; no. 12; pp. 2178 - 2185
• Main Authors: Carroll, Jeffrey B, Warby, Simon C, Southwell, Amber L, Doty, Crystal N, Greenlee, Sarah, Skotte, Niels, Hung, Gene, Bennett, C Frank, Freier, Susan M, Hayden, Michael R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2011; Elsevier Limited; Nature Publishing Group
• Subjects: Alleles; Animals; Apoptosis; Brain - metabolism; Brain - pathology; Cells, Cultured; Chromosomes; Cytomegalovirus; Disease; Female; Fibroblasts - cytology; Fibroblasts - metabolism; Gene Silencing; Genetic Therapy; Humans; Huntingtin Protein; Huntington Disease - genetics; Huntington Disease - therapy; Male; Medicine; Mice; Mice, Transgenic; Mutant Proteins - genetics; Mutation; Nerve Tissue Proteins - genetics; Neurodegeneration; Neurons - metabolism; Neurons - pathology; Nuclear Proteins - genetics; Oligonucleotides, Antisense - therapeutic use; Original; Pedigree; Polymorphism; Polymorphism, Single Nucleotide - genetics; Proteins; Research centers; RNA, Messenger - genetics; Serotonin Plasma Membrane Transport Proteins - chemistry; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin Plasma Membrane Transport Proteins - metabolism; Trinucleotide Repeat Expansion - genetics; Canada; California; Vancouver British Columbia Canada; United States > US

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild-...