Neuronal activation stimulates cytomegalovirus promoter-driven transgene expression

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http://hdl.handle.net/10138/312752

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Bäck , S , Dossat , A , Parkkinen , I , Koivula , P , Airavaara , M , Richie , C T , Chen , Y-H , Wang , Y & Harvey , B K 2019 , ' Neuronal activation stimulates cytomegalovirus promoter-driven transgene expression ' , Molecular therapy-Methods & clinical development , vol. 14 , pp. 180-188 . https://doi.org/10.1016/j.omtm.2019.06.006

Title: Neuronal activation stimulates cytomegalovirus promoter-driven transgene expression
Author: Bäck, Susanne; Dossat, Amanda; Parkkinen, Ilmari; Koivula, Pyry; Airavaara, Mikko; Richie, Christopher T.; Chen, Yun-Hsiang; Wang, Yun; Harvey, Brandon K.
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Neuroscience Center
Date: 2019-09-13
Language: eng
Number of pages: 9
Belongs to series: Molecular therapy-Methods & clinical development
ISSN: 2329-0501
URI: http://hdl.handle.net/10138/312752
Abstract: The cytomegalovirus (CMV) immediate early promoter has been extensively developed and exploited for transgene expression in vitro and in vivo, including human clinical trials. The CMV promoter has long been considered a stable, constitutive and ubiquitous promoter for transgene expression. Using two different CMV-based promoters, we found an increase in CMV-driven transgene expression in the rodent brain and in primary neuronal cultures in response to methamphetamine, glutamate, kainic acid, and activation of G-protein coupled receptor signaling using designer receptors exclusively activated by designer drugs (DREADDs). In contrast, promoters derived from human synapsin 1 (hSyn1) gene or elongation factor 1a (EF1a) did not exhibit altered transgene expression in response to the same neuronal stimulation. Overall, our results suggest that the long standing assertion that the CMV promoter confers constitutive expression in neurons should be reevaluated and future studies should evaluate the activity of the CMV promoter in a given application.
Subject: 3112 Neurosciences
IMMEDIATE-EARLY GENE
NF-KAPPA-B
TRANSCRIPTION FACTORS
DNA-BINDING
METHAMPHETAMINE
SEROTYPE-1
ENHANCER
THERAPY
VECTOR
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