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.