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Multi-unit ribozyme-mediated cleavage of bcr-abl mRNA in myeloid leukemias
LH Leopold, SK Shore, TA Newkirk, RM Reddy and EP Reddy
Temple University Hospital, Philadelphia, PA, USA.
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-unti 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 follic 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.
Volume 85,
Issue 8,
pp. 2162-2170,
04/15/1995
Copyright © 1995 by The American Society of Hematology
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