High-level expression from a cytomegalovirus promoter in macrophage cells

Human Gene Therapy
N RameshW R Osborne

Abstract

To identify vectors that provide optimal gene expression in human hematopoietic cells, we investigated retroviruses containing the adenosine deaminase (ADA) gene under the transcriptional control of the promoters/enhancers of Moloney murine leukemia virus and the human cytomegalovirus (CMV) immediate-early gene. ADA expression was monitored in transduced human multipotential promyelocytic leukemic HL-60 cells and human monocytic leukemic THP-1 cells. HL-60 cells can be induced by phorbol ester to differentiate into macrophage lineage cells and by retinoic acid into granulocytic cells. THP-1 cells undergo phorbol ester-induced differentiation to macrophage cells. In LNCA-transduced HL-60 derived macrophage cells, ADA controlled by the CMV promoter was expressed at 100.0 mumol/hr.mg, in contrast to 1.2 mumol/hr.mg from LN-transduced control cells. LNCA-transduced THP-1 macrophage cells showed a similar increase in ADA activity over control cells. These elevated enzyme activities were confirmed by Northern blots, which showed substantial increases in ADA mRNA derived from the CMV promoter. This suggests use of the CMV promoter for gene therapy targeted at macrophages, as, for example, in the treatment of lysosomal storage disorder...Continue Reading

References

Jun 11, 1992·Nature·A D Miller
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