Heat-inducible vectors for use in gene therapy

The objectives of this study were to quantity and compare the activities of a minimal heat shock (HS) promoter and other promoters used in gene therapy applications, and to identify strategies to amplify the heat inducibility of therapeutic genes. Human tumour cells were transiently or stably transf...

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Veröffentlicht in:International journal of hyperthermia 2000, Vol.16 (2), p.171-181
Hauptverfasser: Gerner, E. W., Hersh, E. M., Pennington, M., Tsang, T. C., Harris, D., Vasanwala, F., Brailey, J.
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container_end_page 181
container_issue 2
container_start_page 171
container_title International journal of hyperthermia
container_volume 16
creator Gerner, E. W.
Hersh, E. M.
Pennington, M.
Tsang, T. C.
Harris, D.
Vasanwala, F.
Brailey, J.
description The objectives of this study were to quantity and compare the activities of a minimal heat shock (HS) promoter and other promoters used in gene therapy applications, and to identify strategies to amplify the heat inducibility of therapeutic genes. Human tumour cells were transiently or stably transfected with the HS promoter driving expression of reporter genes. HS promoter activity was induced transiently, with maximum activity 16-24 h after HS, and was dependent on temperature. The activity of the minimal HS promoter was similar, after 420C HS for 1 h, to that of the cytomegalovirus (CMV) promoter. To determine if the HS promoter could be used to activate a second conditional promoter, cells were transiently transfected with vectors containing both the HS and human immunodeficiency virus type 1 (HIV1) promoters. When the IL-2 gene was placed downstream of the HIV1 promoter, IL-2 production was temperature-independent. The addition of the HIV tat gene downstream of the HS promoter caused IL-2 to be induced more than 3 fold after a single 420C HS. These data indicate that the minimal HS promoter, following activation by clinically attainable temperatures (>=420C), can drive expression of therapeutic genes at levels comparable to the CMV promoter and be used in conjunction with a second conditional promoter to drive temperature-dependent, gene expression.
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subjects AIDS/HIV
Biological and medical sciences
Biotechnology
Fundamental and applied biological sciences. Psychology
Gene therapy
Genes, tat
Genetic Therapy
Genetic Vectors
Green Fluorescent Proteins
Health. Pharmaceutical industry
Heat Shock
Promoter
Gene Expression
HIV-1 - genetics
HSP70 Heat-Shock Proteins - genetics
Humans
Hyperthermia, Induced
Industrial applications and implications. Economical aspects
Interleukin-2 - genetics
Luminescent Proteins - genetics
Promoter Regions, Genetic
Tumor Cells, Cultured
title Heat-inducible vectors for use in gene therapy
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