title: Gene therapy for adenosine deaminase deficiency.
abstract: The clinical gene therapy trials for adenosine deaminase (ADA) deficiency have defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indicate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC can engraft in nonmyeloablated patients, (c) the frequency of HSC transduction/engraftment is low (1/10,000), (d) an in vivo selective advantage can exist for transduced T lymphoid progeny, and (e) the transduced ADA gene is not expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC will require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transduction.
authors.affiliation: Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, California, USA. rparkman@chla.usc.edu
authors.forename: R
authors.initials: R
authors.lastname: Parkman
authors.forename: K
authors.initials: K
authors.lastname: Weinberg
authors.forename: G
authors.initials: G
authors.lastname: Crooks
authors.forename: J
authors.initials: J
authors.lastname: Nolta
authors.forename: N
authors.initials: N
authors.lastname: Kapoor
authors.forename: D
authors.initials: D
authors.lastname: Kohn
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency*; D000818:Animals; D016026:Bone Marrow Transplantation; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D005312:Fetal Blood; D005353:Fibronectins; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007154:Immune System Diseases / Q000628:therapy; D016086:Lentivirus; D051379:Mice; D013601:T-Lymphocytes / Q000637:transplantation
chemical_list: D005353:Fibronectins; D018844:Cyclin-Dependent Kinases; D000243:Adenosine Deaminase