PMID: 12788652Jun 6, 2003Paper

Optimization of transgene expression at the posttranscriptional level in neural cells: implications for gene therapy

Molecular Therapy : the Journal of the American Society of Gene Therapy
Sophie BrunJacques Mallet

Abstract

Gene delivery vectors need to fulfill several efficacy and safety criteria before they can be used in humans. Successful clinical application requires effective transgene expression with a minimum of vector-associated toxicity. We describe the use of posttranscriptional regulatory elements in plasmid and lentiviral vectors coding for luciferase. These constructs allow high-level gene expression in both neuronal and glial cells. Of the several elements that we tested, WPRE gave the highest level of expression. Further enhancements were obtained when WPRE was combined with sequences corresponding to the 3' or 5' untranslated regions (UTR) of eukaryotic mRNAs (tau 3'UTR, TH 3'UTR, and APP 5'UTR). In neuronal cells, WPRE and both tau 3'UTR and APP 5'UTR had an additive effect on expression. The combination of the three elements increased the basal level of expression by up to 26-fold. In glial cells, WPRE and APP 5'UTR had additive effects on expression, and their combination increased expression up to 10-fold. These results provide important information regarding the development of optimal CNS gene transfer vectors not only for gene therapy but also for the study of gene function.

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Citations

Jan 6, 2011·Genetic Vaccines and Therapy·Nicolas GrandchampChamsy Sarkis
Nov 16, 2010·Future Microbiology·Patrick MaierStephanie Laufs
Nov 11, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stéphanie PhilippeChe Serguera
Nov 7, 2007·Journal of Neuroscience Methods·Sergio GascónFrancisco G Scholl
May 26, 2007·Biochemical and Biophysical Research Communications·T ArányiJ Mallet
Jan 30, 2016·The Journal of Gene Medicine·Laura Mantoan RitterMary Collins
Apr 18, 2012·The Biochemical Journal·Toshie SakumaYasuhiro Ikeda
Aug 13, 2013·Neuroscience Letters·Jiong DaiJi-Yao Jiang
Apr 6, 2007·Nature·Feng ZhangKarl Deisseroth
Jan 19, 2020·Nature Communications·Hiroyuki KabayamaKatsuhiko Mikoshiba
Nov 10, 2007·Progress in Biophysics and Molecular Biology·Laurent Nottale, Charles Auffray

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