title: Suppression of transthyretin expression by ribozymes: a possible therapy for familial amyloidotic polyneuropathy.
abstract: Familial amyloidotic polyneuropathy type 1 (FAP) is an autosomal-dominantly inherited disorder with systemic deposition of a variant transthyretin (TTR). We attempted to suppress TTR production by ribozyme degradation of TTR mRNA. Hammerhead and hairpin ribozymes cleaved TTR mRNA at specific individual sites in vitro. A ribozyme targeting a variant TTR (E61K) degraded the variant mRNA, but not a wild-type mRNA. These ribozymes also reduced the amounts of TTR mRNA and protein in HepG2 cells and COS-1 cells transfected with TTR-E61K cDNA. Ribozymes might be studied further as a potential treatment for FAP.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Ohyagi
authors.forename: H
authors.initials: H
authors.lastname: Asahara
authors.forename: I
authors.initials: I
authors.lastname: Horiuchi
authors.forename: J
authors.initials: J
authors.lastname: Kira
mesh_terms: D017772:Amyloid Neuropathies / Q000188:drug therapy / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D011228:Prealbumin / Q000187:drug effects* / Q000378:metabolism; D016337:RNA, Catalytic / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011228:Prealbumin; D016337:RNA, Catalytic; D012333:RNA, Messenger