Efficient c-kit receptor-targeted gene transfer to primary human CD34-Selected hematopoietic stem cells

We have previously reported effective gene transfer with a targeted molecul ar conjugate adenovirus vector through the c-kit receptor in hematopoietic progenitor cell lines. However, a c-kit-targeted recombinant retroviral vec tor failed to transduce cells, indicating the existence of significant diff erences for c-kit target gene transfer between these two viruses. Here we d emonstrate that conjugation of an adenovirus to a c-kit-retargeted retrovir us vector enables retroviral transduction. This finding suggests the requir ement of endosomalysis for successful c-kit-targeted gene transfer. Further more, we show efficient gene transfer to, and high transgene expression (66 %) in, CD34-selected, c-kit(+) human peripheral blood stem cells using a c- kit-targeted adenovirus vector. These findings may have important implicati ons for future vector development in c-kit-targeted stem cell gene transfer .