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Neuronal Activation Stimulates Cytomegalovirus Promoter-Driven Transgene Expression.


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 1? (EF1?) did not exhibit altered transgene expression in response to the same neuronal stimulations. 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 empirically determine the activity of the CMV promoter in a given application.

SUBMITTER: Back S 

PROVIDER: S-EPMC6661544 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Neuronal Activation Stimulates Cytomegalovirus Promoter-Driven Transgene Expression.

Bäck Susanne S   Dossat Amanda A   Parkkinen Ilmari I   Koivula Pyry P   Airavaara Mikko M   Richie Christopher T CT   Chen Yun-Hsiang YH   Wang Yun Y   Harvey Brandon K BK  

Molecular therapy. Methods & clinical development 20190703


The cytomegalovirus (CMV) immediate early promoter has been extensively developed and exploited for transgene expression <i>in vitro</i> and <i>in vivo</i>, 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, k  ...[more]

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