Evaluation of lymphoid-specific enhancer addition or substitution in a basic retrovirus vector.
Two novel retroviral vectors bearing lymphoid-specific enhancers were tested for improved expression of human adenosine deaminase (hADA) in tissue culture cells and in mouse bone marrow transplant recipients. These vectors carried either an added human T-cell receptor alpha-chain enhancer (delta N2TADA) or a substitution of the Moloney long terminal repeat (LTR) enhancer with the murine immunoglobulin mu heavy-chain first intron enhancer (delta N2 mu ADA). Each vector was produced at a titer of approximately 10(6) infectious units/ml and efficiently transduced hADA into murine fibroblast and myeloma cells in culture. No quantitative difference in expression was observed between the enhancer modified vectors and the basic retrovirus vector (delta N2ADA). In addition, each vector efficiently conferred hADA expression in lymphoid, myeloid, and erythroid cells of long-term transplanted mice. The majority of the transduced-marrow recipients demonstrated expression of the human enzyme for 4-8 months with each of the three vectors.
Moore
K A
KA
Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.
Scarpa
M
M
Kooyer
S
S
Utter
A
A
Caskey
C T
CT
Belmont
J W
JW
D000243:Adenosine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts; D015967:Gene Expression Regulation, Viral; D005819:Genetic Markers; D005822:Genetic Vectors; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008979:Moloney murine leukemia virus / Q000235:genetics; D009101:Multiple Myeloma / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012190:Retroviridae / Q000235:genetics*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D005819:Genetic Markers; D007148:Immunoglobulin mu-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D000243:Adenosine Deaminase