Evaluation of HBV promoters for use in hepatic gene therapy.
Strategies for in vivo hepatic gene therapy will require regulatory elements which allow for long-term expression of therapeutic genes and restriction of expression to hepatocytes. This study investigates the suitability of promoters derived from hepatitis B virus (HBV) for liver-specific gene expression in vectors for hepatic gene therapy. We provide three hepatocyte-specific promoters, the HBV core promoter, the HBV core promoter linked directly to the HBV enhancer I, and a hybrid promoter containing the HBV enhancer II and a basic CMV promoter, which are hepatocyte-specific and allow for increasing levels of reporter gene expression. Moreover, in long-term expression studies using our promoter constructs in the context of an EBV based expression system we found that expression from these promoters remained nearly unchanged over a period of at least two months in hepatocyte-derived cell lines.
Löser
P
P
Max-Planck-Gesellschaft, Humboldt-Universität, Berlin-Buch, Germany.
Sandig
V
V
Kirillova
I
I
Strauss
M
M
D016475:3T3 Cells; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005069:Evaluation Studies as Topic; D017930:Genes, Reporter; D015316:Genetic Therapy; D006367:HeLa Cells; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D000956:Antigens, Viral; D006512:Hepatitis B Core Antigens; D017874:Immediate-Early Proteins; C044582:immediate-early proteins, cytomegalovirus; D008156:Luciferases; D001616:beta-Galactosidase