title: Expression vectors for human adenosine deaminase gene therapy.
abstract: Somatic gene transfer offers a possible new approach for treatment of human genetic disease. Defects affecting blood-forming tissues are candidates for therapies involving transfer of genetic information into hematopoietic stem cells. Adenosine deaminase (ADA) deficiency is being used as a model disease for which gene transfer techniques can be developed and evaluated. We describe here the construction and testing of 20 retroviral vectors for their ability to transfer and express human ADA in vitro and in vivo via a mouse bone marrow transplantation model. After infection of primary bone marrow with one fo these vectors (p delta NN2ADA), human ADA was detected in 60-85% of spleen colonies at day 14 and maintained long term in the blood of fully reconstituted mice. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells.
authors.affiliation: Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.
authors.forename: K A
authors.initials: KA
authors.lastname: Moore
authors.forename: F A
authors.initials: FA
authors.lastname: Fletcher
authors.forename: R L
authors.initials: RL
authors.lastname: Alford
authors.forename: D K
authors.initials: DK
authors.lastname: Villalon
authors.forename: D H
authors.initials: DH
authors.lastname: Hawkins
authors.forename: G R
authors.initials: GR
authors.lastname: MacGregor
authors.forename: C T
authors.initials: CT
authors.lastname: Caskey
authors.forename: J W
authors.initials: JW
authors.lastname: Belmont
mesh_terms: D000243:Adenosine Deaminase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D015316:Genetic Therapy; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009700:Nucleoside Deaminases / Q000235:genetics*; D011828:Radiation Chimera; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D012190:Retroviridae
chemical_list: D011993:Recombinant Fusion Proteins; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase