Research ExplorerPublicationsLentiviral HSV-Tk.007-mediated suicide gene therapy is not t...

Lentiviral HSV-Tk.007-mediated suicide gene therapy is not toxic for normal brain cells

Standard

Lentiviral HSV-Tk.007-mediated suicide gene therapy is not toxic for normal brain cells. / Hossain, Jubayer A; Ystaas, Lars Rømo; Mrdalj, Jelena; Välk, Kristjan; Riecken, Kristoffer; Fehse, Boris; Bjerkvig, Rolf; Grønli, Janne; Miletic, Hrvoje.

In: J GENE MED, Vol. 18, No. 9, 09.2016, p. 234-43.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hossain, JA, Ystaas, LR, Mrdalj, J, Välk, K, Riecken, K, Fehse, B, Bjerkvig, R, Grønli, J & Miletic, H 2016, 'Lentiviral HSV-Tk.007-mediated suicide gene therapy is not toxic for normal brain cells', J GENE MED, vol. 18, no. 9, pp. 234-43. https://doi.org/10.1002/jgm.2895

APA

Hossain, J. A., Ystaas, L. R., Mrdalj, J., Välk, K., Riecken, K., Fehse, B., Bjerkvig, R., Grønli, J., & Miletic, H. (2016). Lentiviral HSV-Tk.007-mediated suicide gene therapy is not toxic for normal brain cells. J GENE MED, 18(9), 234-43. https://doi.org/10.1002/jgm.2895

Vancouver

Hossain JA, Ystaas LR, Mrdalj J, Välk K, Riecken K, Fehse B et al. Lentiviral HSV-Tk.007-mediated suicide gene therapy is not toxic for normal brain cells. J GENE MED. 2016 Sep;18(9):234-43. https://doi.org/10.1002/jgm.2895

Bibtex

@article{f591ebea63174d32b114bc242bf92d63,
title = "Lentiviral HSV-Tk.007-mediated suicide gene therapy is not toxic for normal brain cells",
abstract = "BACKGROUND: Gene therapeutic strategies with suicide genes are currently investigated in clinical trials for brain tumors. Previously, we have shown that lentiviral vectors delivering the suicide gene HSV-Tk to experimental brain tumors promote a highly significant treatment effect and thus are promising vectors for clinical translation.METHODS: In the present study, we tested lentiviral vectors delivering the suicide gene HSV-Tk.007, a highly active mutant of HSV-Tk, to rat brains as a preclinical toxicity study. We injected 10(6) vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped functional lentiviral particles harboring the suicide gene HSV-Tk.007 into the brain of healthy, immunocompetent rats. During prodrug treatment with ganciclovir (GCV), we measured weight and assessed the behavior of the rats in an open field test. After 14 days of GCV treatment, we analyzed HSV-Tk.007 expression in different brain cell populations, as well as inflammatory responses and apoptosis.RESULTS: During prodrug treatment with GCV, behavior experiments did not reveal differences between the treated rats and the control groups. Analysis of HSV-Tk expression in different brain cell populations showed that transduced normal brain cells survived GCV treatment. There were no statistically significant differences in the number of transduced cells between treatment and control groups. Furthermore, inflammatory responses and apoptosis of brain cells were not observed.CONCLUSIONS: We show that HSV-Tk.007-mediated suicide gene therapy is not toxic to normal brain cells. This observation is of high relevance for the translation of lentivirus-mediated suicide gene therapies into the clinic for the treatment of brain tumor patients. Copyright {\textcopyright} 2016 John Wiley & Sons, Ltd.",
keywords = "Journal Article",
author = "Hossain, {Jubayer A} and Ystaas, {Lars R{\o}mo} and Jelena Mrdalj and Kristjan V{\"a}lk and Kristoffer Riecken and Boris Fehse and Rolf Bjerkvig and Janne Gr{\o}nli and Hrvoje Miletic",
note = "Copyright {\textcopyright} 2016 John Wiley & Sons, Ltd.",
year = "2016",
month = sep,
doi = "10.1002/jgm.2895",
language = "English",
volume = "18",
pages = "234--43",
journal = "J GENE MED",
issn = "1099-498X",
publisher = "John Wiley and Sons Ltd",
number = "9",

}

RIS

TY - JOUR

T1 - Lentiviral HSV-Tk.007-mediated suicide gene therapy is not toxic for normal brain cells

AU - Hossain, Jubayer A

AU - Ystaas, Lars Rømo

AU - Mrdalj, Jelena

AU - Välk, Kristjan

AU - Riecken, Kristoffer

AU - Fehse, Boris

AU - Bjerkvig, Rolf

AU - Grønli, Janne

AU - Miletic, Hrvoje

N1 - Copyright © 2016 John Wiley & Sons, Ltd.

PY - 2016/9

Y1 - 2016/9

N2 - BACKGROUND: Gene therapeutic strategies with suicide genes are currently investigated in clinical trials for brain tumors. Previously, we have shown that lentiviral vectors delivering the suicide gene HSV-Tk to experimental brain tumors promote a highly significant treatment effect and thus are promising vectors for clinical translation.METHODS: In the present study, we tested lentiviral vectors delivering the suicide gene HSV-Tk.007, a highly active mutant of HSV-Tk, to rat brains as a preclinical toxicity study. We injected 10(6) vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped functional lentiviral particles harboring the suicide gene HSV-Tk.007 into the brain of healthy, immunocompetent rats. During prodrug treatment with ganciclovir (GCV), we measured weight and assessed the behavior of the rats in an open field test. After 14 days of GCV treatment, we analyzed HSV-Tk.007 expression in different brain cell populations, as well as inflammatory responses and apoptosis.RESULTS: During prodrug treatment with GCV, behavior experiments did not reveal differences between the treated rats and the control groups. Analysis of HSV-Tk expression in different brain cell populations showed that transduced normal brain cells survived GCV treatment. There were no statistically significant differences in the number of transduced cells between treatment and control groups. Furthermore, inflammatory responses and apoptosis of brain cells were not observed.CONCLUSIONS: We show that HSV-Tk.007-mediated suicide gene therapy is not toxic to normal brain cells. This observation is of high relevance for the translation of lentivirus-mediated suicide gene therapies into the clinic for the treatment of brain tumor patients. Copyright © 2016 John Wiley & Sons, Ltd.

AB - BACKGROUND: Gene therapeutic strategies with suicide genes are currently investigated in clinical trials for brain tumors. Previously, we have shown that lentiviral vectors delivering the suicide gene HSV-Tk to experimental brain tumors promote a highly significant treatment effect and thus are promising vectors for clinical translation.METHODS: In the present study, we tested lentiviral vectors delivering the suicide gene HSV-Tk.007, a highly active mutant of HSV-Tk, to rat brains as a preclinical toxicity study. We injected 10(6) vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped functional lentiviral particles harboring the suicide gene HSV-Tk.007 into the brain of healthy, immunocompetent rats. During prodrug treatment with ganciclovir (GCV), we measured weight and assessed the behavior of the rats in an open field test. After 14 days of GCV treatment, we analyzed HSV-Tk.007 expression in different brain cell populations, as well as inflammatory responses and apoptosis.RESULTS: During prodrug treatment with GCV, behavior experiments did not reveal differences between the treated rats and the control groups. Analysis of HSV-Tk expression in different brain cell populations showed that transduced normal brain cells survived GCV treatment. There were no statistically significant differences in the number of transduced cells between treatment and control groups. Furthermore, inflammatory responses and apoptosis of brain cells were not observed.CONCLUSIONS: We show that HSV-Tk.007-mediated suicide gene therapy is not toxic to normal brain cells. This observation is of high relevance for the translation of lentivirus-mediated suicide gene therapies into the clinic for the treatment of brain tumor patients. Copyright © 2016 John Wiley & Sons, Ltd.

KW - Journal Article

U2 - 10.1002/jgm.2895

DO - 10.1002/jgm.2895

M3 - SCORING: Journal article

C2 - 27490042

VL - 18

SP - 234

EP - 243

JO - J GENE MED

JF - J GENE MED

SN - 1099-498X

IS - 9

ER -