In Vitro Purging Of CML By Multi-unit Ribozymes Specific To Bcr-abl

Chronic myeloid leukemia (CML) is a malignant disease of human hematopoietic stem cell, accounting for 20% of leukemias in adult. So far there is no effective treatment to put the majority of CML patients under control. In the pathogenesis of CML, a 210 Kd protein encoded by bcr-abl fusion gene plays a critical role. It has an elevated and disregulated tyrosine kinase activity. Seeing that bcr-abl fusion gene, a result of 9; 22 chromosome reciprocal translocation is regarded as the main cause of CML, this fusion gene is the main target in the gene therapy of CML.Autologous bone marrow transplantation is a hopeful method to cure CML. Improved in vitro purging efficiency of residual leukemia may bring about long-term restoration of Ph-negative hematopoiesis following the clinical application of autologous BMT. The bcr-abl specific ribozymes is a potential gene therapy way in CML because these ribozymes can cleave the fusion gene mRNA and inhibit the expression of p210 protein. So, ribozymes can help effectively purge bone marrow cells in vitro.To investigate the effects of bcr-abl specific triple-unit ribozymes on CML cell line and to further discuss the mechanism and possibility of clinical application of ribozymes, we conducted the following experiments.1 Construction of serial bcr-abl specific ribozymes vectors: Firstly, 3...