Long-term expression of human adenosine deaminase in mice after transplantation of bone marrow infected with amphotropic retroviral vectors.
Three retroviral vectors, containing a human adenosine deaminase (ADA) cDNA linked to either the simian virus 40 (SV40) early promoter, the human cytomegalovirus (CMV) immediate early promoter, or the Moloney murine leukemia virus (MoMLV) promoter, were tested for their ability to express ADA following infection and transplantation of murine bone marrow. Virus was produced by using PA317 amphotropic retrovirus packaging cells. The titer of each of the vectors was similar and no helper virus was detected. Human ADA was expressed in the blood of some animals for 6 months after transplantation of infected marrow, and vector DNA was found in the spleen and in bone marrow from these animals. The percentage of animals expressing human ADA (33%) and the amount of human ADA in blood (1-5% of total ADA) was similar for each of the vectors. These results show that amphotropic vectors are capable of infecting pluripotent hematopoietic stem cells having long-term repopulating ability, and that a variety of promoters allow gene expression following differentiation of these early cells.
Osborne
W R
WR
Department of Pediatrics, University of Washington, Seattle 98195.
Hock
R A
RA
Kaleko
M
M
Miller
A D
AD
D000243:Adenosine Deaminase / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000201:enzymology / Q000382:microbiology; D016026:Bone Marrow Transplantation; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005822:Genetic Vectors; D006378:Helper Viruses / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012190:Retroviridae / Q000235:genetics*; D013997:Time Factors
D004279:DNA, Viral; D015345:Oligonucleotide Probes; D000243:Adenosine Deaminase