Ribozyme-mediated cleavage of the BCRABL oncogene transcript: in vitro cleavage of RNA and in vivo loss of P210 protein-kinase activity.

The t(9,22) chromosomal translocation generating the Philadelphia chromosome and the BCRABL oncogene has been shown both cytogenetically and molecularly to be the etiologic event in chronic myelogenous leukemia (CML). We have designed a ribozyme to cleave the BCRABL mRNA by targeting a GUU triplet adjacent to the junction of the c-BCR and c:ABL fused genes. This ribozyme efficiently cleaved BCRABL RNA transcripts as demonstrted by in vitro cleavage reactions. To determine the effect of constitutive expression of the ribozyme on the elimination of the BCRABL gene product, the ribozyme cDNA sequence was inserted into different retroviral expression vectors