Differential influence of the E4 adenoviral genes on viral and cellular promoters
| Autor: | Anne-Isabelle Michou, Monika Lusky, Linda Grave, A Dieterle, Majid Mehtali, Andrea Pavirani, Cecile Doderer, Pierre Leroy, Dominique Dreyer |
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| Rok vydání: | 2000 |
| Předmět: |
Transcription
Genetic Transgene Genetic enhancement Genetic Vectors Cytomegalovirus Mice Inbred Strains Mice SCID Biology Cell Line law.invention Mice Transcription (biology) In vivo law Chlorocebus aethiops Drug Discovery Tumor Cells Cultured Genetics Animals Humans Transgenes Northern blot Promoter Regions Genetic Vero Cells Molecular Biology Gene Genetics (clinical) Gene Transfer Techniques Promoter 3T3 Cells Molecular biology Avian Sarcoma Viruses Gene Expression Regulation COS Cells Recombinant DNA Adenovirus E1 Proteins Molecular Medicine Gene Deletion Adenovirus E4 Proteins HeLa Cells |
| Zdroj: | The Journal of Gene Medicine. 2:433-443 |
| ISSN: | 1521-2254 1099-498X |
| Popis: | Background Strong and stable transgene expression is fundamental to the success of recombinant adenovirus vectors in human gene therapy. However, control of transgene expression is a complex process, involving both viral and cellular factors. In this study, the influence of the E4 adenoviral region on the activity of various promoters was investigated in vitro and in vivo. Methods Pairs of isogenic E1° and E1°E4° vectors were generated and compared. Levels of transgene expression were determined by Northern blot, ELISA and FACS analysis. Initiation of transcription was studied by nuclear run-on assays. Results Similar to the viral CMV and RSV promoters, the activity of the ubiquitous cellular PGK promoter required the presence of the E4 genes in vitro and in vivo. In contrast, transgene expression from selected liver- and tumor-specific promoters did not require E4 functions. Conclusion Together with the reported low liver toxicity of E1°E4° vectors, the independence of E4 of liver-specific promoters renders such vectors interesting alternatives to the use of gutless vectors. Copyright © 2000 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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