Production of human glucocerebrosidase in mice after retroviral gene transfer into multipotential hematopoietic progenitor cells

Journal Article · Tue Oct 31 23:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.22.8912· OSTI ID:6906453

Correll, P H; Fink, J K; Brady, R O; Perry, L K; Karlsson, S ^[1]

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1. National Institutes of Health, Bethesda, MD (USA)

The human glucocerebrosidase (GC) gene has been transferred efficiently into spleen colony-forming unit (CFU-S) multipotential hematopoietic progenitor cells, and production of human GC RNA and protein has been achieved in transduced CFU-S colonies. High-titer retroviral vectors containing the human GC cDNA were constructed. Four vectors were compared with respect to gene-transfer efficiency into CFU-S progenitors. One vector (G vector) required high concentrations of interleukins 3 and 6 during stimulation and coculture for efficient transduction of CFU-S progenitors. The remaining three vectors (NTG, GTN, and GI vectors) transduced these progenitors at infection frequencies approaching 100% using low concentrations of hematopoietic growth factors to simulate cell division prior to and during the infection. Vectors using the viral long terminal repeat enhancer/promoter to drive the human GC cDNA produced high levels of human GC RNA in the progeny of CFU-S progenitors after gene transfer. All three vectors producing human GC RNA in CFU-S colonies can generate human GC as detected by immunochemical analysis of CFU-S colonies. The capacity of the viral long terminal repeat and the internal thymidine kinase promoter to direct synthesis of RNA in transduced bone marrow and spleen cells 5 months after bone marrow transplantation reflected the performance of these promoters in NTG-transduced CFU-S colonies.

• OSTI ID: 6906453
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:22; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550401* -- Genetics-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTIBODIES
BIOCHEMISTRY
BODY
BONE MARROW CELLS
CFU
CHEMISTRY
CONNECTIVE TISSUE CELLS
CYTOCHEMISTRY
DISEASES
DNA
DNA POLYMERASES
ENZYMES
GENE RECOMBINATION
GENE REGULATION
GENE REPRESSORS
GLYCOSYL HYDROLASES
GROWTH FACTORS
HEMATOPOIETIC SYSTEM
HEREDITARY DISEASES
HERPES SIMPLEX
HYDROLASES
INFECTIOUS DISEASES
IRRADIATION
LETHAL IRRADIATION
LYMPHOKINES
MACROPHAGES
MAMMALS
MESSENGER-RNA
MICE
MICROORGANISMS
MITOGENS
MONOCLONAL ANTIBODIES
NUCLEIC ACIDS
NUCLEOPROTEINS
NUCLEOTIDYLTRANSFERASES
O-GLYCOSYL HYDROLASES
ORGANIC COMPOUNDS
ORGANS
PARASITES
PHAGOCYTES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PROTEINS
RECOMBINANT DNA
RNA
RODENTS
SKIN DISEASES
SOMATIC CELLS
SPLEEN
THERAPY
TRANSFERASES
VERTEBRATES
VIRAL DISEASES
VIRUSES