Journal article
Authors list: Kaestle, Christine; Winkeler, Alexandra; Richter, Raphaela; Sauer, Heinrich; Hescheler, Juergen; Fraefel, Cornel; Wartenberg, Maria; Jacobs, Andreas H.
Publication year: 2011
Pages: 197-205
Journal: Molecular Imaging
Volume number: 10
Issue number: 3
ISSN: 1535-3508
Open access status: Gold
DOI Link: https://doi.org/10.2310/7290.2010.00036
Publisher: SAGE 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.
Citation Styles
Harvard Citation style: Kaestle, 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 Citation style: Kaestle, 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
Keywords
ADENOVIRAL VECTORS; BRAIN-TUMORS; confocal microscopy; CONVECTION-ENHANCED DELIVERY; LASER-SCANNING MICROSCOPY; LIMITED EFFICACY; MALIGNANT GLIOMAS; MULTICELLULAR SPHEROIDS
