In vivo transduction of primitive mobilized hematopoietic stem cells after intravenous injection of integrating adenovirus vectors.

ABSTRACT: Current protocols for hematopoietic stem/progenitor cell (HSPC) gene therapy, involving the transplantation of ex vivo genetically modified HSPCs are complex and not without risk for the patient. We developed a new approach for in vivo HSPC transduction that does not require myeloablation and transplantation. It involves subcutaneous injections of granulocyte-colony-stimulating factor/AMD3100 to mobilize HSPCs from the bone marrow (BM) into the peripheral blood stream and the IV injection of an integrating, helper-dependent adenovirus (HD-Ad5/35⁺⁺) vector system. These vectors target CD46, a receptor that is uniformly expressed on HSPCs. We demonstrated in human CD46 transgenic mice and immunodeficient mice with engrafted human CD34⁺ cells that HSPCs transduced in the

SUBMITTER: Richter M 

PROVIDER: S-EPMC5095755 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature