Human gene expression in murine hemopoietic cells in vivo.

Abstract

Somatic gene transfer offers the possibility of a new approach in the treatment of human genetic disease. Defects affecting the blood and blood forming tissues are candidates for therapies involving transfer of new genetic information into hemopoietic stem cells. One such defect, adenosine deaminase (ADA) deficiency, is being used as a model in which hemopoietic gene transfer techniques can be developed and evaluated. In this model, gene transfer is mediated by a retroviral vector. Retroviral vectors have been used extensively to deliver information to hemopoietic cells1–14. We have previously reported delivery and expression of human ADA (hADA) sequences in murine hemopoietic progenitors in vitro15 and in vivo16, but were not able to demonstrate long term stability of expression. We describe here the construction and testing of four new vectors, representing the first demonstration of efficient transfer and long term in vivo expression of hADA in murine hemopoietic cells.