Provided herein are retargeted foamy virus (FV) vectors, including insulated retargeted FV vectors such as 650cHS4, Al, and A2 insulator retargeted FV vectors that exhibit high, clinically significant titers, favorable safety profiles, and reduced genotoxicity. The retargeted FV vectors disclosed herein may be suitably employed for therapeutic applications, in particular gene therapy applications, which involve the ex vivo and/or in vivo delivery of a gene of interest to a wide variety of target cells, including hematoietic cells, such as hematopoietic progenitor cells and stem cells (HSCs).