Open AccessExpression of human adenosine deaminase in mice reconstituted with retrovirus-transduced hematopoietic stem cells.
Author(s) -
James M. Wilson,
Olivier Danos,
Mariann Grossman,
David H. Raulet,
Richard C. Mulligan
Publication year - 1990
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.87.1.439
Subject(s) - adenosine deaminase , haematopoiesis , stem cell , biology , transplantation , genetic enhancement , hematopoietic stem cell transplantation , severe combined immunodeficiency , retrovirus , adenosine deaminase deficiency , peripheral blood mononuclear cell , virology , viral vector , bone marrow , microbiology and biotechnology , immunology , recombinant dna , cancer research , gene , adenosine , virus , medicine , genetics , in vitro , biochemistry
Recombinant retroviruses encoding human adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) have been used to infect murine hematopoietic stem cells. In bone marrow transplant recipients reconstituted with the genetically modified cells, human ADA was detected in peripheral blood mononuclear cells of the recipients for at least 6 months after transplantation. In animals analyzed in detail 4 months after transplantation, human ADA and proviral sequences were detected in all hematopoietic lineages; in several cases, human ADA activity exceeded the endogenous activity. These studies demonstrate the feasibility of introducing a functional human ADA gene into hematopoietic stem cells and obtaining expression in multiple hematopoietic lineages long after transplantation. This approach should be helpful in designing effective gene therapies for severe combined immunodeficiency syndromes in humans.