NDLI: Retroviral vector-mediated high-efficiency expression of adenosine deaminase (ADA) in hematopoietic long-term cultures of ADA-deficient marrow cells.

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Retroviral vector-mediated high-efficiency expression of adenosine deaminase (ADA) in hematopoietic long-term cultures of ADA-deficient marrow cells.

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Retroviral vector-mediated high-efficiency expression of adenosine deaminase (ADA) in hematopoietic long-term cultures of ADA-deficient marrow cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Keever, C. A. Gilboa, E. Hantzopoulos, P. O'reilly, R. J. Bordignon, C. Yu, S. F. Ungers, G. E. Smith, C. A.
Description	Author Affiliation: Bordignon C ( Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.);
Abstract	Two recombinant retroviral vectors encoding the cDNA of the human adenosine deaminase (ADA; EC 3.5.4.4) gene and the bacterial neomycin resistance (Neo) gene have been used to transduce bone marrow cells obtained from four patients affected by the ADA-deficient variant of severe combined immunodeficiency. By utilizing the long-term marrow culture system, freshly isolated bone marrow cells were subjected to multiple infection cycles with cell-free supernatants containing high titers of viral vector and then maintained in long-term marrow culture in the absence of any overt selection pressure. By using this experimental protocol, about 30-40% of the hematopoietic progenitors were productively transduced with the viral vector, as judged by the appearance of G418-resistant colonies derived from granulocyte/macrophage and multipotent hematopoietic progenitor cells. The vector-encoded human ADA gene was expressed efficiently in both the myeloid and lymphoid progeny of the cultured bone marrow cells, reaching levels between 15% and 100% as compared to the levels of ADA in normal bone marrow cells. The efficiency of gene transfer and ADA production was proportional to the number of infection cycles. Furthermore, transduction of the ADA vectors into the bone marrow cells derived from an ADA-deficient patient restored the capacity of the cells to respond to phytohemagglutinin and interleukin 2.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	86
Language	English
Publisher	National Academy of Sciences
Publisher Date	1989-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adenosine Deaminase Genetics Bone Marrow Enzymology Genetic Vectors Hematopoietic Stem Cells Immunologic Deficiency Syndromes Nucleoside Deaminases Simian Virus 40 Biosynthesis Deficiency Pathology Cell Differentiation Cells, Cultured Cytology Transduction, Genetic Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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