Human fetal mesenchymal stem cells (hfMSC) demonstrate extensive expansion and differentiation capacities and are hence being studied for use in stem cell therapeutics, including gene delivery. With advanced prenatal diagnosis, fetal gene therapy represents an additional avenue for the treatment of inherited deficiencies. We have recently demonstrated harvesting of first-trimester fMSC from fetal blood for ex vivo genetic engineering to introduce genes of interest, and finally intra-uterine transplantation (IUT) of these cells to the fetus. Here we discuss methods in the harvesting of hfMSC, lentiviral transduction to introduce genes of interest, and in vitro methods to characterise transgene expression.