MULTIUNIT RIBOZYME-MEDIATED CLEAVAGE OF BCR-ABL MESSENGER-RNA IN MYELOID LEUKEMIAS

被引:68
作者
LEOPOLD, LH
SHORE, SK
NEWKIRK, TA
REDDY, RMV
REDDY, EP
机构
[1] FELS INST CANC RES & MOLEC BIOL, PHILADELPHIA, PA USA
[2] TEMPLE UNIV HOSP & MED SCH, PHILADELPHIA, PA USA
关键词
D O I
10.1182/blood.V85.8.2162.bloodjournal8582162
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Chronic myelogenous leukemia is characterized by the Philadelphia chromosome, which at the molecular level results from the fusion of the bcr gene on chromosome 22 and the abl gene on chromosome 9. The bcr-abl fusion gene encodes a novel tyrosine kinase with transforming activity, In this study, we have synthesized a multi-unit ribozyme that targets bcr-abl mRNA. In vitro ribozyme cleavage reactions show increased cleavage efficiency of this multi-unit ribozyme compared with single or double ribozymes. The multiunit ribozyme was then transfected into murine myeloblasts transformed with the bcr-abl gene (32D cells). Ribozyme transfection was accomplished either by liposomes or using folic acid-polylysine as a carrier. Multi-unit ribozyme transfection reduced the level of bcr-abl mRNA 3 logs when transfected via folate receptor-mediated uptake into transformed 32D cells. These results suggest that a multi-unit ribozyme could be an effective therapeutic agent for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia. (C) 1995 by The American Society of Hematology.
引用
收藏
页码:2162 / 2170
页数:9
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