Neuronal activation stimulates cytomegalovirus promoter-driven transgene expression

Susanne Bäck, Amanda Dossat, Ilmari Parkkinen, Pyry Koivula, Mikko Airavaara, Christopher T. Richie, Yun-Hsiang Chen, Yun Wang, Brandon K. Harvey

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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.
Alkuperäiskielienglanti
LehtiMolecular therapy-Methods & clinical development
ISSN2329-0501
DOI - pysyväislinkit
TilaJulkaistu - 2019
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3112 Neurotieteet

Lainaa tätä

Bäck, Susanne ; Dossat, Amanda ; Parkkinen, Ilmari ; Koivula, Pyry ; Airavaara, Mikko ; Richie, Christopher T. ; Chen, Yun-Hsiang ; Wang, Yun ; Harvey, Brandon K. / Neuronal activation stimulates cytomegalovirus promoter-driven transgene expression. Julkaisussa: Molecular therapy-Methods & clinical development. 2019.
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title = "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 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.",
keywords = "3112 Neurosciences",
author = "Susanne B{\"a}ck and Amanda Dossat and Ilmari Parkkinen and Pyry Koivula and Mikko Airavaara and Richie, {Christopher T.} and Yun-Hsiang Chen and Yun Wang and Harvey, {Brandon K.}",
year = "2019",
doi = "10.1016/j.omtm.2019.06.006",
language = "English",
journal = "Molecular therapy-Methods & clinical development",
issn = "2329-0501",
publisher = "Nature Publishing Group",

}

Neuronal activation stimulates cytomegalovirus promoter-driven transgene expression. / Bäck, Susanne; Dossat, Amanda; Parkkinen, Ilmari; Koivula, Pyry; Airavaara, Mikko; Richie, Christopher T.; Chen, Yun-Hsiang; Wang, Yun; Harvey, Brandon K.

julkaisussa: Molecular therapy-Methods & clinical development, 2019.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Neuronal activation stimulates cytomegalovirus promoter-driven transgene expression

AU - Bäck, Susanne

AU - Dossat, Amanda

AU - Parkkinen, Ilmari

AU - Koivula, Pyry

AU - Airavaara, Mikko

AU - Richie, Christopher T.

AU - Chen, Yun-Hsiang

AU - Wang, Yun

AU - Harvey, Brandon K.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - 3112 Neurosciences

U2 - 10.1016/j.omtm.2019.06.006

DO - 10.1016/j.omtm.2019.06.006

M3 - Article

JO - Molecular therapy-Methods & clinical development

JF - Molecular therapy-Methods & clinical development

SN - 2329-0501

ER -