title: Inhibition of mutant huntingtin expression by RNA duplex targeting expanded CAG repeats.
abstract: The specific silencing of the gene of interest is the major objective of RNA interference technology; therefore, unique sequences but not abundant sequence repeats are targeted by silencing reagents. Here, we describe the targeting of expanded CAG repeats that occur in transcripts derived from the mutant allele of the gene implicated in Huntington's disease (HD) in the presence of the normal allele and other human mRNAs containing CAG and CUG repeat tracts. We show that a high degree of silencing selectivity may be achieved between the repeated sequences. We demonstrate preferential suppression of the mutant huntingtin allele and concomitant activation of the normal huntingtin allele in cell lines derived from HD patients that were transfected with short RNA duplexes composed of CAG and CUG repeats containing mutations at specific positions. These effects may lead to promising therapeutic modalities for HD, a condition for which no therapy presently exists.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704, Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Fiszer
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Mykowska
authors.forename: Wlodzimierz J
authors.initials: WJ
authors.lastname: Krzyzosiak
mesh_terms: D000483:Alleles; D002478:Cells, Cultured; D006801:Humans; D000071058:Huntingtin Protein; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000737:chemistry; D012333:RNA, Messenger / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry; D019680:Trinucleotide Repeat Expansion
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering