Gene transfer for the eventual treatment of Fanconi's anemia.

Aplastic anemia can be either acquired or congenital. The paradigm for the congenital form is Fanconi's anemia (FA). FA is an autosomal recessive, genetic syndrome characterized by progressive bone marrow failure, developmental abnormalities, and a predisposition to malignancy. The clinical manifestations of FA are heterogeneous, but one common outcome in the majority of patients is the development of life-threatening hematologic disease. FA is thought to affect the hematopoietic stem cell, and the hematologic consequences of FA can be effectively treated by complete replacement of patient stem cells by those from a histocompatible donor. Unfortunately, allogeneic stem cell transplantation is currently limited to patients with an unaffected matched sibling donor. Transplantation from alternative donors, while successful in selected cases, is associated with a high risk of graft failure and must be carefully considered in terms of risk and benefit for each individual. For FA patients lacking an appropriate donor, new therapies need to be devised. This review summarizes both the scientific rationale and the progress of gene therapy strategies aimed at correcting the hematopoietic defect of FA.