The goal of this program project is to develop new and safe approaches for stem cell therapy in general and stem cell gene therapy for the beta-chain hemoglobinopathies, sickle cell anemia and homozygous beta-thalassemia, in particular. The program consists of six projects and four core units. The objective of Project by Stamatoyannopoulos is to develop new chromatin insulators for use in gene therapy vectors and investigate the functions of globin gene oncoretrovirus, foamy virus, lentivirus and Adeno AAV vectors in the primate transplantation model. Projects by Russell and Lieber focus on the development of new vector technologies for stem cell gene therapy; foamy viral vectors (Project by Russell); and deleted adeno AAV vectors containing the whole beta-globin gene locus control region (Project by Lieber). Success in the development of these new vectors will have a major impact on the field of stem cell gene therapy. Project by Blau uses a new technology, based on chemical inducers of dimerization, to achieve in vivo selection of genetically modified stem cells. Project by Kiem studies oncoretroviral and lentiviral vectors in the baboon model and attempts new approaches for improving stem cell engraftment. Project by Naldini focuses on the investigation of new approaches that will increase the efficiency and safety of lentiviral vectors. The NOD/SCID Mouse Core is a SCID/NOD mice unit and will assist investigators in the assessment of gene transfer into human hemopoietic stem cells. The Genomics Core is a genomic unit and will assist the projects with sequencing and functional analyses of viral vector investigation sites. The Large Animal Core will perform bone marrow transplantation in large animals (primates and dogs), to assess gene transfer into the hemopoietic stem cells. The Administration Core will provide administrative support.
| Constantinou, Varnavas C; Bouinta, Asimina; Karponi, Garyfalia et al. (2017) Poor stem cell harvest may not always be related to poor mobilization: lessons gained from a mobilization study in patients with ?-thalassemia major. Transfusion 57:1031-1039 |
| Gori, Jennifer L; Butler, Jason M; Kunar, Balvir et al. (2017) Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates. Stem Cells Transl Med 6:864-876 |
| Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia (2016) Optimizing autologous cell grafts to improve stem cell gene therapy. Exp Hematol 44:528-39 |
| Li, Li B; Ma, Chao; Awong, Geneve et al. (2016) Silent IL2RG Gene Editing in Human Pluripotent Stem Cells. Mol Ther 24:582-91 |
| Karponi, Garyfalia; Psatha, Nikoletta; Lederer, Carsten Werner et al. (2015) Plerixafor+G-CSF-mobilized CD34+ cells represent an optimal graft source for thalassemia gene therapy. Blood 126:616-9 |
| Vierstra, Jeff; Reik, Andreas; Chang, Kai-Hsin et al. (2015) Functional footprinting of regulatory DNA. Nat Methods 12:927-30 |
| Qi, Heyuan; Liu, Mingdong; Emery, David W et al. (2015) Functional validation of a constitutive autonomous silencer element. PLoS One 10:e0124588 |
| Liu, Mingdong; Maurano, Matthew T; Wang, Hao et al. (2015) Genomic discovery of potent chromatin insulators for human gene therapy. Nat Biotechnol 33:198-203 |
| Polak, Paz; Karli?, Rosa; Koren, Amnon et al. (2015) Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature 518:360-364 |
| Deyle, David R; Hansen, R Scott; Cornea, Anda M et al. (2014) A genome-wide map of adeno-associated virus-mediated human gene targeting. Nat Struct Mol Biol 21:969-75 |
Showing the most recent 10 out of 161 publications
