Barcoding of Macaque Hematopoietic Stem and Progenitor Cells: A Robust Platform to Assess Vector Genotoxicity.

ABSTRACT: Gene therapies using integrating retrovirus vectors to modify hematopoietic stem and progenitor cells have shown great promise for the treatment of immune system and hematologic diseases. However, activation of proto-oncogenes via insertional mutagenesis has resulted in the development of leukemia. We have utilized cellular bar coding to investigate the impact of different vector designs on the clonal behavior of hematopoietic stem and progenitor cells (HSPCs) during in vivo expansion, as a quantitative surrogate assay for genotoxicity in a non-human primate model with high relevance for human biology. We transplanted two rhesus macaques with autologous CD34+ HSPCs transduced with three lentiviral vectors containing different promoters and/or enhancers of a predicted range of genoto

SUBMITTER: Yabe IM 

PROVIDER: S-EPMC6258888 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature