RIBOZYME-MEDIATED CLEAVAGE OF THE BCR ABL TRANSCRIPT EXPRESSED IN CHRONIC MYELOID-LEUKEMIA/

The brr/abl transcript is specifically expressed in the hematopoietic cells of patients with chronic myeloid leukemia (CML). The Haseloff an d Gerlach model was used to design a ribozyme targeted to this transcr ipt. When tested against a synthetic substrate covering the translocat ion sequence, the ribozyme exhibited site specificity and an absolute requirement for divalent metal ions. Cleavage of the normal bcr was al so noted but at a reduced efficiency compared to that exhibited for th e brr/abl substrate. Importantly, cleavage of the full-length bcr/abl mRNA was achieved at physiologic temperature, demonstrating effective ribozyme-mediated cleavage.