CHIMERIC DNA/RNA RIBOZYMES CONTAINING PROPANEDIOL

摘要

DNA-RNA-(Pr)n-RNA-DNA ribozymes of formula (III) 5' Z-cugaugag-(Pr)n-cgaaa-X 3'; or (IV) 3'X-aaagc-(Pr)n-gaguaguc-Z-R-Z-cugaugag-(Pr)n-cgaaa-X 3' in which X and Z comprise DNA sequences that base pair with an RNA substrate at positions adjacent to an RNA cleavage site; cugaugag and cgaaa are catalytic RNA sequences; Pr is a spacer residue -P(O) (OH)-O-CH2CH2CH2-O-; and R is a bridging residue of -O-CH2-C(CH2OH) (CH3)-CH2-O-. The ribozymes can be made on any DNA synthesizer using phosphoramidite chemistry, and are useful as therapeutic agents for treating viral or endogenous RNA-mediated diseases. Preferred ribozymes target a sequence in the U5 region of HIV-1.