High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors.
By virtue of its immediate contact with the circulating blood, the endothelium provides an attractive target for retroviral vector transduction for the purpose of gene therapy. To see whether efficient gene transfer and expression was feasible, rabbit aortic endothelial cells were infected with three Moloney murine leukemia virus-derived retroviral vectors. Two of these vectors carry genes encoding products that are not secreted: N2, containing only the selectable marker gene neoR, and SAX, containing both neoR gene and an SV40-promoted adenosine deaminase (ADA) gene. The third vector, G2N, contains a secretory rat growth hormone (rGH) gene and an SV40-promoted neoR gene. Infection with all three vectors resulted in expression of the respective genes. A high level of human ADA expression was observed in infected endothelial cell populations both before and after selection in G418. G2N-infected rabbit aortic endothelial cells that were grown on a synthetic vascular graft continued to secrete rGH into the culture medium. These studies suggest that endothelial cells may serve as vehicles for the introduction in vivo of functioning recombinant genes.
Zwiebel
J A
JA
Laboratory of Molecular Hematology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Freeman
S M
SM
Kantoff
P W
PW
Cornetta
K
K
Ryan
U S
US
Anderson
W F
WF
D000243:Adenosine Deaminase / Q000032:analysis / Q000235:genetics; D000818:Animals; D001011:Aorta; D004274:DNA, Recombinant / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005796:Genes; D005814:Genes, Viral; D005819:Genetic Markers / Q000032:analysis; D005822:Genetic Vectors; D013006:Growth Hormone / Q000032:analysis / Q000235:genetics; D008979:Moloney murine leukemia virus / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis; D014161:Transduction, Genetic; D014162:Transfection
D004274:DNA, Recombinant; D005819:Genetic Markers; D011994:Recombinant Proteins; D013006:Growth Hormone; D000243:Adenosine Deaminase