Large animal models of hematopoietic stem cell gene therapy

摘要: Large animal models have been instrumental in advancing hematopoietic stem cell (HSC) gene therapy. Here we review the advantages of large models, their contributions to field HSC therapy and recent progress this field. Several properties human HSCs including purification, cell-cycle characteristics, response cytokines proliferative demands placed on them after transplantation are more similar than mice. Progress development use retroviral vectors ex vivo transduction protocols over last decade has led efficient transfer both dogs nonhuman primates. Importantly, approaches developed these translated well clinic. animals continue be useful evaluate efficacy safety therapy, with diseases now cured by Nonhuman primates allow evaluation aspects as disease-specific such AIDS (acquired immunodeficiency syndrome) that can not modeled dog. Finally, used genotoxicity viral comparing integration sites repopulating cells monitoring clonality transplantation.