title: Modulation of beta-secretase gene expression by action of catalytic nucleic acids.
abstract: Two sites of the initial translation sequence of beta-secretase (BACE) mRNA were chosen as targets for endogenously delivered hammerhead ribozymes. Ribozyme cassettes coding a catalytic core, flanked by the 5'-tRNA(Val) and the 3'-CTE (constitutive transport element) sequences, were cloned into a pUC119 plasmid and used for transfection of transformed primary human embryonal kidney (HEK293) cells. The ribozymes express in the test cells and inhibit beta-secretase gene biosynthesis on the level of mRNA (up to 95%) and on the level of protein (up to 90%) and thus may be considered as therapeutic inhibitors of beta-secretase activity.
authors.affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nawrot
authors.forename: Slawomir
authors.initials: S
authors.lastname: Antoszczyk
authors.forename: Maria
authors.initials: M
authors.lastname: Maszewska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rebowski
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuwabara
authors.forename: Masaki
authors.initials: M
authors.lastname: Warashina
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
authors.forename: Wojciech J
authors.initials: WJ
authors.lastname: Stec
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D002384:Catalysis; D010450:Endopeptidases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D009696:Nucleic Acids / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009696:Nucleic Acids; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human