PMID- 14644505
OWN - NLM
STAT- MEDLINE
DCOM- 20040217
LR  - 20190708
IS  - 0378-1119 (Print)
IS  - 0378-1119 (Linking)
VI  - 322
DP  - 2003 Dec 11
TI  - Chimeric transcriptional control units for improved liver-specific transgene 
      expression.
PG  - 137-43
AB  - Hepatocyte-directed delivery of therapeutic genes is a major field of gene 
      therapy. An important issue in this context is the availability of promoters 
      units providing for maximum transcriptional activity and specificity. Although a 
      number of liver-specific promoters and transcriptional control elements have been 
      identified and used for gene delivery, no systematic study has been performed to 
      identify the best suitable combination of known liver-specific promoter and 
      enhancer elements. We now report the results of a comparative investigation 
      addressing this issue. We tested a total of 25 synthetic transcriptional control 
      units consisting of either of the four core promoters from liver-specific genes 
      linked in various combinations and configurations to hepatocyte-specific enhancer 
      elements. These constructs were analyzed for transcriptional activity in 
      different cell types in cell culture and in mouse liver in vivo. The data lead to 
      the clear conclusion that a combination of the alcohol dehydrogenase 6 (ADH6) 
      basal promoter linked to two tandem copies of an apoplipoprotein E enhancer 
      element is the transcriptional control unit of choice for the liver-specific 
      expression of transgenes.
FAU - Gehrke, Stephan
AU  - Gehrke S
AD  - Institute of Molecular Biology and Tumor Research, Philipps-University, 
      Emil-Mannkopff-Strasse 2, 35033 Marburg, Germany.
FAU - Jerome, Valerie
AU  - Jerome V
FAU - Muller, Rolf
AU  - Muller R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (alpha 1-Antitrypsin)
RN  - 9001-28-9 (Factor IX)
RN  - EC 1.1.1.1 (Alcohol Dehydrogenase)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase)
SB  - IM
MH  - Alcohol Dehydrogenase/genetics
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cholesterol 7-alpha-Hydroxylase/genetics
MH  - Enhancer Elements, Genetic/genetics
MH  - Factor IX/genetics
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Injections, Intravenous
MH  - Liver/*metabolism
MH  - Luciferases/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Nude
MH  - Plasmids/administration & dosage/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Recombinant Fusion Proteins/administration & dosage/genetics/*metabolism
MH  - Transcription, Genetic/genetics
MH  - Transfection
MH  - Transgenes/*genetics
MH  - alpha 1-Antitrypsin/genetics
EDAT- 2003/12/04 05:00
MHDA- 2004/02/18 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/02/18 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - S0378111903008709 [pii]
AID - 10.1016/j.gene.2003.08.010 [doi]
PST - ppublish
SO  - Gene. 2003 Dec 11;322:137-43. doi: 10.1016/j.gene.2003.08.010.