Retroviral vector interactions with hematopoietic cells

•Cocal envelope pseudotype has low toxicity, broad tropism and resists human sera.•The small molecule drug rapamycin can be used to increase transduction efficiency.•Novel promoters or miRNAs can target transgene expression.•Foamy vector integration can be retargeted into heterochromatin to improve safety.

Hematopoietic stem cell (HSC) gene therapy using retroviral vectors is a powerful and promising approach to permanently correct many hematopoietic disorders. Increasing the transduction of quiescent HSCs and reducing genotoxicity are major challenges in the field. Retroviral vectors, including lentiviral and foamy vectors, have been extensively modified resulting in improved safety and efficacy. This review will focus on recent advances to improve vector entry, transduction efficiency, control of transgene expression and approaches to improve safety by modifying the retroviral integration profile.