Hammerhead ribozyme and DNAzyme that can specifically cleave leukemogenic TEL-AML1 chimeric mRNA
2006. 11. 15
301-520, 16:00-17:00 PM
Functional hammerhead ribozyme can be designed to cleave any target RNA in trans by generating RNA molecules with sequences reverse complementary to a target RNA. Similar to the hammerhead ribozyme, a class of antisense oligodeoxynucleotides, known as the ¡°10-23¡± DNAzyme, which is a small catalytic DNA, has been shown to efficiently cleave target RNA at purine-pyrimidine junctions in vitro. We synthesized several RNA-cleaving DNAzymes and hammerhead ribozymes, which are targeted to the leukemogenic TEL-AML1 chimeric RNA. Three DNA enzymes and one hammerhead ribozyme demonstrated their efficient RNA-cleavage activity and specificity in vitro. The selected DNAzyme and hammerhead ribozyme, when introduced into mammalian cells that were transiently transfected with the TEL-AML1 fusion gene, efficiently decreased expression of the leukemogenic TEL-AML1 mRNA and protein. Thus, both hammerhead ribozyme and DNAzyme that targeted TEL-AML1 chimeric mRNA will be potentially useful as gene-inactivating agents for the treatment of leukemia.
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