A single adenovirus vector mediates doxycycline-controlled expression of tyrosine hydroxylase in brain grafts of human neural progenitors

Ex vivo gene transfer is emerging as a promising therapeutic approach to human neurodegenerative diseases. By combining efficient methodologies for cell amplification and gene delivery, large numbers of cells can be generated with the capacity to synthesize therapeutic molecules. These cells can the...

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Veröffentlicht in:Nature biotechnology 1999-04, Vol.17 (4), p.349-354
Hauptverfasser: Mallet, Jacques, Corti, Olga, Sabaté, Olivier, Horellou, Philippe, Colin, Philippe, Dumas, Sylvie, Buchet, Delphine, Buc-Caron, Marie-Hélène
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container_end_page 354
container_issue 4
container_start_page 349
container_title Nature biotechnology
container_volume 17
creator Mallet, Jacques
Corti, Olga
Sabaté, Olivier
Horellou, Philippe
Colin, Philippe
Dumas, Sylvie
Buchet, Delphine
Buc-Caron, Marie-Hélène
description Ex vivo gene transfer is emerging as a promising therapeutic approach to human neurodegenerative diseases. By combining efficient methodologies for cell amplification and gene delivery, large numbers of cells can be generated with the capacity to synthesize therapeutic molecules. These cells can then be transplanted into the degenerating central nervous system (CNS). Applying this approach to human diseases will require the development of suitable cellular vehicles, as well as safe gene delivery systems capable of tightly controlled transgene expression. For such brain repair technologies, human neural progenitors may be extremely valuable, because of their human CNS origin and developmental potential. We have used these cells to develop a system for the regulated expression of a gene of therapeutic potential. We report the construction of a single adenovirus encoding human tyrosine hydroxylase 1 (hTH-1) under the negative control of the tetracycline-based gene regulatory system. Human neural progenitors infected with this vector produced large amounts of hTH-1. Most importantly, doxycycline allowed a reversible switch of transgene transcription both in vitro and in vivo. This system may be applied to the development of therapies for human neurodegenerative diseases.
doi_str_mv 10.1038/7901
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subjects Adenoviridae - genetics
Agriculture
Animals
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Brain - cytology
Brain - embryology
Brain - enzymology
Brain Tissue Transplantation
Cell Transplantation
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Doxycycline - pharmacology
Fetal Tissue Transplantation
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Gene therapy
Gene Transfer Techniques
Genetic Vectors
Health. Pharmaceutical industry
Humans
Industrial applications and implications. Economical aspects
Life Sciences
Medical sciences
Neurology
Rats
research-article
Stem Cell Transplantation
Stem Cells - virology
Tyrosine 3-Monooxygenase - biosynthesis
Tyrosine 3-Monooxygenase - genetics
title A single adenovirus vector mediates doxycycline-controlled expression of tyrosine hydroxylase in brain grafts of human neural progenitors
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