Hossle
Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Immunologie, Abteilung » Prof. Dr. Reinhard Seger » Hossle
Completed research project
| Title / Titel | Development of clinically applicable protocols for transitory and permanent somatic gene therapy in chronic granulomatous disease | ||||||
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| Abstract (PDF, 14 KB) | |||||||
| Summary / Zusammenfassung | The objective of our study was the development of clinically applicable protocols for somatic gene therapy in patients with the X-linked primary immunodeficiency chronic granulomatous disease (X-CGD). We have developed a bicistronic retroviral vector (SPsLdS) carrying the therapeutic gp91phox gene and a truncated form of the low affinity nerve growth factor receptor (DLNGFR) as a selectable marker. Using this vector, transduction of CD34+ bone marrow (BM) cells or mobilized peripheral blood CD34+ cells (PBSC) from X-CGD patients resulted in clinically relevant levels of functional correction of X-CGD. The long-term function of SPsLdS was successfully evaluated in the X-CGD knock-out mouse model. Mobilized human CD34+ PBSC transduced with the SPsLdS retroviral vector were successfully tested for engraftment in the NOD/SCID mouse model. The developed retroviral vector SPsLdS was produced under good-manufacturing-practise (GMP) conditions, and has been approved to be used in a clinical phase I study. Most recent further progress included i) lentiviral vector constructs for gene transfer into even more primitive quiescent stem cells and ii) successful assembly of a human G-CSFR/estrogen chimeric receptor for to provide transduced progenitor cells with a selection advantage. |
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| Publications / Publikationen | Becker S, S Wasser, M Hauses, JP Hossle, MG Ott, MC Dinauer, A Ganser, D Hoelzer, R Seger, and M Grez. 1998. Correction of respiratory burst activity in X-linked chronic granulomatous cells to therapeutically relevant levels after gene transfer into bone marrow CD34+ cells. Hum. Gen. Ther. 9:1561-1570.Schneider SD, S Rusconi, RA Seger, and JP Hossle. 1997. Adenovirus-mediated gene transfer into monocyte-derived macrophages of patients with X-linked chronic granulomatous disease: ex vivo correction of deficient respiratory burst. Gene Therapy 4:524-532.Schwarz K, S Nonoyama, MC Peitsch, G de Saint Basile, T Espanol, A Fasth, A Fischer, K Freitag, W Friedrich, S Fugmann, JP Hossle, A Jones, C Kinnon, A Meindl, L Notarangelo, A Wechsler, M Weiss, HD Ochs. 1996. WASPbase: a database of mutations causing the Wiskott-Aldrich Syndrome (WAS) and X-linked Thrombocytopenia (XLT). Immunology Today 17:496-502. | ||||||
| Keywords / Suchbegriffe | Chronic granulomatous disease (CGD), phagocytes, bone marrow cells, retroviral vector, somatic gene therapy | ||||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.unifr.ch/nfp37/ | ||||||
| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Oct 1996 to Jun 2000 |