Figure 1. Approach for the genetic manipulation of hematopoietic stem cells (HSCs).
The upper panel compares the predictive value and accessibility of various preclinical models in the evaluation of gene transfer efficiency and insertional genotoxicity of vectors used in HSC gene therapy trials. The lower panel depicts the optimized protocol for transduction of hematopoietic stem and progenitor cells, as used in recent clinical trials.
BM (bone marrow); Flt3L (fms-related tyrosine kinase 3 ligand); FN (fibronectin); IL3 (interleukin 3); MGDF (megakaryocyte growth and development factor); MLV (murine leukemia virus); MPBC (mobilized peripheral blood cells); SCF (stem cell factor); SIN (self-inactivating); TPO (thrombopoietin)