PMID- 10207882
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20131121
IS  - 1087-0156 (Print)
IS  - 1087-0156 (Linking)
VI  - 17
IP  - 4
DP  - 1999 Apr
TI  - A single adenovirus vector mediates doxycycline-controlled expression of tyrosine 
      hydroxylase in brain grafts of human neural progenitors.
PG  - 349-54
AB  - 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.
FAU - Corti, O
AU  - Corti O
AD  - Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus 
      Neurodegeneratifs, C.N.R.S., Hopital de la Pitie Salpetriere, Paris, France.
FAU - Sabate, O
AU  - Sabate O
FAU - Horellou, P
AU  - Horellou P
FAU - Colin, P
AU  - Colin P
FAU - Dumas, S
AU  - Dumas S
FAU - Buchet, D
AU  - Buchet D
FAU - Buc-Caron, M H
AU  - Buc-Caron MH
FAU - Mallet, J
AU  - Mallet J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Biotechnol
JT  - Nature biotechnology
JID - 9604648
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Brain/*cytology/embryology/enzymology
MH  - *Brain Tissue Transplantation
MH  - Cell Transplantation
MH  - Doxycycline/pharmacology
MH  - Fetal Tissue Transplantation
MH  - Gene Expression Regulation
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors
MH  - Humans
MH  - Rats
MH  - *Stem Cell Transplantation
MH  - Stem Cells/virology
MH  - Tyrosine 3-Monooxygenase/biosynthesis/*genetics
EDAT- 1999/04/20 02:03
MHDA- 2001/03/23 10:01
CRDT- 1999/04/20 02:03
PHST- 1999/04/20 02:03 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/04/20 02:03 [entrez]
AID - 10.1038/7901 [doi]
PST - ppublish
SO  - Nat Biotechnol. 1999 Apr;17(4):349-54. doi: 10.1038/7901.