Hossle
Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Immunologie, Abteilung » Prof. Dr. Reinhard Seger » Hossle
Completed research project
| Title / Titel | Gene therapy in children with X-linked chronic granulomatous disease (CGD) | ||||||
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| Abstract (PDF, 14 KB) | |||||||
| Summary / Zusammenfassung | The project is directed at a stem cell therapy for permanent genetic correction of X-CGD hematopietic stem or progenitor cells (HS/PC) and their progeny, and complementary, an effector cell therapy aiming at the rapid generation of high numbers of genetically corrected therapeutic peripheral blood cells. The previously developed bicistronic retroviral vector SPsLdS is subjected to further preclinical testing i) of the engraftment and multilineage potency of SPsLdS-transduced CGD HS/PC in the human xenograft nod/scid mouse model, and ii) the evaluation of the efficacy of a SPsLdS gene therapy in X-CGD knock-out mice. It is planned to use SPsLdS for first phase I clinical studies. These studies will be either designed as 1) repetitive stem/progenitor (HS/PC) gene therapies using transduced CD34+ cells without conditioning, or 2) gene transfer studies into HS/PC combining mild myelosuppressive chemotherapy with autologous reconstitution, as an entirely novel approach. Furthermore, the project explores the retroviral transduction of estrogen/cytokine receptor chimeras into human HS/PC for selective 4OH-tamoxifen-dependent ex and in vivo expansion and/or differentiation of transduced human CD34+ cells for a transient effector cell therapy. In order to surpass the limitations of the current generation of murine retroviral vectors to transduce early potentially quiescent hematopoietic stem cells (HSC), lentivirus self-inactivating (SIN) vectors are generated. |
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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.Ott MG, M Grez, S Becker, S Wasser, JP Hossle, RA Seger, MC Dinauer, and D Hoelzer. 1998. Towards therapy of chronic granulomatous disease by gene transfer into hematopoietic stem cells. Brit J Haematol 102 Suppl S: 80-81. | ||||||
| Keywords / Suchbegriffe | X-linked chronic granulomatous disease, gene therapy, hematopoietic stem cells, receptor chimera, lentivirus vector | ||||||
| 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 | Jul 1999 to Jun 2001 |