Journalartikel

Imaging Herpes Simplex Virus Type 1 Amplicon Vector-Mediated Gene Expression in Human Glioma Spheroids


AutorenlisteKaestle, Christine; Winkeler, Alexandra; Richter, Raphaela; Sauer, Heinrich; Hescheler, Juergen; Fraefel, Cornel; Wartenberg, Maria; Jacobs, Andreas H.

Jahr der Veröffentlichung2011

Seiten197-205

ZeitschriftMolecular Imaging

Bandnummer10

Heftnummer3

ISSN1535-3508

Open Access StatusGold

DOI Linkhttps://doi.org/10.2310/7290.2010.00036

VerlagSAGE Publications


Abstract
Vectors derived from herpes simplex virus type 1 (HSV-1) have great potential for transducing therapeutic genes into the central nervous system; however, inefficient distribution of vector particles in vivo may limit their therapeutic potential in patients with gliomas. This study was performed to investigate the extent of HSV-1 amplicon vector-mediated gene expression in a three-dimensional glioma model of multicellular spheroids by imaging highly infectious HSV-1 virions expressing green fluorescent protein (HSV-GFP). After infection or microscopy-guided vector injection of glioma spheroids at various spheroid sizes, injection pressures and injection times, the extent of HSV-1 vector-mediated gene expression was investigated via laser scanning microscopy. Infection of spheroids with HSV-GFP demonstrated a maximal depth of vector-mediated GFP expression at 70 to 80 mm. A > 80% transduction efficiency was reached only in small spheroids with a diameter of < 150 mu m. Guided vector injection into the spheroids showed transduction efficiencies ranging between < 10 and > 90%. The results demonstrated that vector-mediated gene expression in glioma spheroids was strongly dependent on the mode of vector application-injection pressure and injection time being the most important parameters. The assessment of these vector application parameters in tissue models will contribute to the development of safe and efficient gene therapy protocols for clinical application.


Zitierstile

Harvard-ZitierstilKaestle, C., Winkeler, A., Richter, R., Sauer, H., Hescheler, J., Fraefel, C., et al. (2011) Imaging Herpes Simplex Virus Type 1 Amplicon Vector-Mediated Gene Expression in Human Glioma Spheroids, Molecular Imaging, 10(3), pp. 197-205. https://doi.org/10.2310/7290.2010.00036

APA-ZitierstilKaestle, C., Winkeler, A., Richter, R., Sauer, H., Hescheler, J., Fraefel, C., Wartenberg, M., & Jacobs, A. (2011). Imaging Herpes Simplex Virus Type 1 Amplicon Vector-Mediated Gene Expression in Human Glioma Spheroids. Molecular Imaging. 10(3), 197-205. https://doi.org/10.2310/7290.2010.00036



Schlagwörter


ADENOVIRAL VECTORSBRAIN-TUMORSconfocal microscopyCONVECTION-ENHANCED DELIVERYLASER-SCANNING MICROSCOPYLIMITED EFFICACYMALIGNANT GLIOMASMULTICELLULAR SPHEROIDS


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