Modulation of beta-secretase gene expression by action of catalytic nucleic acids.
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.
Nawrot
Barbara
B
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.
Antoszczyk
Slawomir
S
Maszewska
Maria
M
Rebowski
Grzegorz
G
Kuwabara
Tomoko
T
Warashina
Masaki
M
Taira
Kazunari
K
Stec
Wojciech J
WJ
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
D009696:Nucleic Acids; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human