Gene therapy for congenital lymphoid immunodeficiency diseases.

The primary immunodeficiencies are a group of rare genetic diseases in which mutations of genes necessary for host defense result in increased susceptibility to infection. In the past 10 years, the genes responsible for most forms of human immunodeficiency have been identified, cloned, and their function and expression have been characterized. The identification of the genes for human immunodeficiencies has generally been the result of cloning efforts directed at specific diseases, rather than the human genome project. During this same period, technology for the delivery of genes to target cells for disease treatment (gene therapy) has also been developed. Because of certain biological features of human immunodeficiency diseases, each is a particularly attractive subject of early clinical trials of gene therapy. The convergence of the advances in gene cloning and gene transfer has led to great interest in the gene therapy of immunodeficiency diseases. This report will review particular aspects of lymphoid immunodeficiency disease as they relate to gene therapy, the preclinical evaluation of gene therapy for these diseases, and the clinical gene therapy trials for adenosine deaminase (ADA) deficiency, the first immunodeficiency to be treated by gene therapy.