Gene therapy for adenosine deaminase deficiency

The clinical gene therapy trials for adenosine deaminase (ADA) deficiency h ave defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indi cate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC ca n engraft in nonmyeloablated patients, (c) the frequency of HSC transductio n/engraftment is low (1/10,000), (d) an in vivo selective advantage can exi st for transduced T lymphoid progeny, and (e) the transduced ADA gene is no t expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC w ill require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transducti on.