Expression of human alpha 1 antitrypsin in murine hematopoietic cells in vivo after retrovirus-mediated gene transfer.

For patients with alpha1 antitrypsin (alpha 1AT) deficiency, the expression of alpha 1AT in hematopoietic cells may results in a number of benefits not provided by gene transfer strategies involving local modification of the respiratory epithelium or liver-directed gene transfer. We investigated the expression of alpha 1AT in murine hematopoietic cells after retrovirus-mediated gene transfer. For this purpose we constructed an LNL-6-derived recombinant retrovirus vector (L alpha 1ED) that expresses the alpha 1AT cDNA from the Moloney murine leukemia virus (MoMuLV) U3 promoter/enhancer and coexpresses the cDNA for a mutant form of the murine dihydrofolate reductase molecule (*DHFR) from the encephalomyocarditis virus (emc) internal ribosome entry site (IRES). All of the mice transplanted with bone marrow transduced with the L alpha 1ED vector expressed the alpha 1AT protein at the 3-week time point after transplantation. By the 6-week time point the alpha 1AT levels declined to a lower level, where they generally remained for the duration of the experiment. This study demonstrates the potential utility of hematopoietic cell gene transfer for gene therapy of alpha 1AT deficiency.