Abstract
For therapeutic purposes, two chimeric DNA/RNA hammerhead ribozymes were synthesized to cleaveAML1/MTG8, the t(8;21)-associated fusion mRNA of acute myeloid leukemia. One ribozyme, A/MRZ-1, recognizes the area adjacent to the fusion point betweenAML1 andMTG8, and cleaves six bases downstream from this point. The other, MRZ-1, recognizes theMTG8 sequence. Both ribozymes cleaved synthetic chimeric DNA/RNA substrates at theoretical sites. Neither cleavedAML1 RNA. A/MRZ-1 cleaved onlyAML1/MTG8 RNA, and MRZ-1 cleaved bothAML1/MTG8 andMTG8 RNAs. The two ribozymes showed growth inhibition of an acute myeloid leukemia cell line carrying t(8;21), SKNO-1 cells. The same extent of growth inhibition was attained by antisense oligonucleotides againstAML1/MTG8 RNA. The results suggest that the ribozyme has the potential to be developed as a useful agent for gene therapy, in particular for leukemia with t(8;21).
Key words: Ribozyme, Acute myeloid leukemia, Gene therapy
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