|
|
|
| |
|
|
> Moritz, Hannover - Modlich, Hannover <
Abstract I
Investigator I
Publications
Humanized models to assess the genotoxicity of viral vectors in the context of hematopoietic stem cell expansion and in vivo selection
So far, the vast majority of preclinical studies addressing genotoxic risks in the context of hematopoietic gene therapy have been performed in murine models. Given the differences between human and murine hematopoiesis this may not be adequate in all situations. We therefore propose to establish model systems directly assessing gene vector related genotoxic risks in human cells. These models will be based on the xenotransplantation of human hematopoietic cells into immunodeficient mice (humanised NOD/SCID/IL2r null model) or the in vitro growth and replating capacity of insertionally activated hematopoietic progenitor/stem cells (In Vitro Immortalisation Assay). We further suggest to utilise these models for preclinical safety analysis of retroviral gene transfer in the context of i) growth factor mediated in vitro expansion of hematopoietic cells and ii) drug resistance based in vivo selection of gene modified cells. Successful completion of the proposed project not only would add valuable new models for genotoxicity analysis of gene vectors to the tool box of the SPP1230 consortium. In addition it would help to better define the risk profile of novel strategies with the potential to influence the future development of hematopoietic gene therapy.
Thomas Moritz, Prof. Dr. med.
Ute Modlich, Dr. med. vet, Ph.D.
5 selected Publications related to the project
Modlich U, Navarro S, Zychlinski D, Maetzig T, Knoess S, Brugman MH, Schambach A, Charrier S, Galy A, Thrasher AJ, Bueren J, Baum C. Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol. Ther. 2009; 17: 1919-28 |
top
dw-websites