Usefulness of a mouse myelin basic protein promoter for gene therapy of malignant glioma: myelin basic protein promoter is strongly active in human malignant glioma cells.
We have searched for suitable promoters to regulate the expression of suicide genes for use in gene therapy. We have shown that the 1.3-kb fragment of the mouse myelin basic protein (MBP) promoter region initiates transcription in mouse glioma cells more efficiently than glial fibrillary acidic protein (GFAP) or myelin proteolipid protein (PLP) promoter. Among three different lengths of the MBP promoter, the shortest (256-bp) core promoter region initiates transcription as efficiently as 650-bp or 1.3-kb MBP promoter lengths in RSV-M glioma cells. To assess the suitability of the MBP promoter for use in clinical trials of malignant glioma gene therapy, we also had to show that it (the 1.3-kb length in this case) is effective in human glioma cells, as well as in murine glioma cells. The activity of the MBP promoter is much higher than that of GFAP or PLP promoter in most human glioma cells, suggesting that the MBP promoter would be best for directing toxic gene expression in gene therapy for patients with malignant glioma. Human glioma cells in which the MBP promoter was strongly active were sensitive to ganciclovir when they were transduced with MBP promoter/herpes simplex virus thymidine kinase gene-bearing retroviruses. In conclusion, retrovirus-targeted gene therapy for malignant glioma using this MBP promoter is a promising candidate for clinical trials.
Miyao
Y
Y
Department of Neurosurgery, Osaka University Medical School.
Shimizu
K
K
Tamura
M
M
Akita
H
H
Ikeda
K
K
Mabuchi
E
E
Kishima
H
H
Hayakawa
T
T
Ikenaka
K
K
D016475:3T3 Cells; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D006801:Humans; D051379:Mice; D004676:Myelin Basic Protein / Q000235:genetics*; D018991:Myelin Proteolipid Protein / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D013937:Thymidine Kinase