Despite the gratifying progress, it remains challenging to achieve optimal gene transfer to human HSCs, and 10- to 100-fold higher amounts of vectors are typically needed for their gene modification compared with transduction of cell lines, mesenchymal stem cells, and many other target cell types. This is perhaps most relevant to efforts toward gene therapy of hemoglobinopathies, where the large, complex human β-globin gene cassettes needed for high-level, erythroid-specific expression lead to lower vector titers and limit gene transfer efficacy, in contrast to what can be achieved with vectors carrying simple cDNA and small promoter elements.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141502/
