Gene therapy for primary immunodeficiency disease.

Abstract

Gene therapy offers the potential for developing innovative new treatments for both inherited monogenic diseases as well as polygenic and acquired disorders. For most potential clinical applications, the technology has not yet progressed to the stage where it might be reasonably tested. Problems to be solved include the isolation and characterization of the genes involved, the development of gene delivery systems that will permit efficient gene insertion in the affected cells and tissues, and the development of mechanisms to control or appropriately regulate expression of the introduced genes. The primary immunodeficiency diseases as a group actually lend themselves to the development of gene therapy strategies with current technology more readily than almost any other class of disease. Theoretically any genetic disease that can be successfully treated by allogeneic bone marrow transplantation is a potential candidate for gene therapy directed at correcting the patient's own totipotent bone marrow stem cells. In addition, some disorders lend themselves to genetic correction of more mature cells, although gene transfer in this treatment strategy might have to be repeated periodically. The rationale and preliminary results of the first gene therapy protocol for ADA deficiency SCID are described and strategies for developing somatic cell gene therapy for the other primary immunodeficiency diseases are discussed.