A majority of mice show long-term expression of a human. beta. -globin gene after retrovirus transfer into hematopoietic stem cells

Journal Article · Sat Apr 01 00:00:00 EST 1989 · Molecular and Cellular Biology; (USA)

DOI:https://doi.org/10.1128/MCB.9.4.1426· OSTI ID:5600641

Bender, M A ^[1]; Gelinas, R E; Miller, ^[2]

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1. Washington Univ., Seattle, WA (USA). Dept. of Pathology
2. Fred Hutchinson Cancer Research Center, Seattle, WA (USA)

Murine bone marrow was infected with a high-titer retrovirus vector containing the human {beta}-globin and neomycin phosphotransferase genes. Anemic W/W/sup v/ mice were transplanted with infected marrow which in some cases had been exposed to the selective agent G418. Human {beta}-globin expression was monitored in transplanted animals by using a monoclonal antibody specific for human {beta}-globin polypeptide, and hematopoietic reconstitution was monitored by using donor and recipient mice which differed in hemoglobin type. In some experiments all transplanted mice expressed the human {beta}-globin polypeptide for over 4 months, and up to 50% of peripheral erythrocytes contained detectable levels of polypeptide. DNA analysis of transplanted animals revealed that virtually every myeloid cell contained a provirus. Integration site analysis and reconstitution of secondary marrow recipients suggested that every mouse was reconstituted with at least one infected stem cell which had extensive repopulation capability. The ability to consistently transfer an active {beta}-globin gene into mouse hematopoietic cells improves the feasibility of using these techniques for somatic cell gene therapy in humans.

• OSTI ID: 5600641
• Journal Information: Molecular and Cellular Biology; (USA), Vol. 9:4; ISSN 0270-7306
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLOBIN
GENES
PHOSPHOTRANSFERASES
STEM CELLS
GENETIC ENGINEERING
BONE MARROW
ERYTHROCYTES
HUMAN POPULATIONS
MICE
MONOCLONAL ANTIBODIES
NEOMYCIN
PHENOTYPE
POLYPEPTIDES
SENSITIVITY
SOMATIC CELLS
THERAPY
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
DRUGS
ENZYMES
HEMATOPOIETIC SYSTEM
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PHOSPHORUS-GROUP TRANSFERASES
POPULATIONS
PROTEINS
RODENTS
TISSUES
TRANSFERASES
VERTEBRATES
550400* - Genetics