title: Expression of human alpha 1 antitrypsin in murine hematopoietic cells in vivo after retrovirus-mediated gene transfer.
abstract: 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.
authors.affiliation: Arkansas Children's Hospital, Department of Pediatrics, Little Rock 72202, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Saylors
authors.forename: D A
authors.initials: DA
authors.lastname: Wall
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D004247:DNA / Q000032:analysis; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D012190:Retroviridae / Q000235:genetics*; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis* / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000628:therapy
chemical_list: D000515:alpha 1-Antitrypsin; D004247:DNA