Progress toward gene therapy.
The prospect of treating human disease at its most fundamental (i.e., genetic) level has been the dream of clinicians for decades. There are over 4000 distinct genetic diseases, many of which are debilitating or fatal and most of which are incurable by standard medical approaches. Initial research was directed toward gene replacement treatment of genetic diseases involving the bone marrow, such as sickle cell anemia. Efficient methods for gene transfer were developed, but as this research progressed it became apparent that the biology of the bone marrow stem cell and the regulation of hemoglobin synthesis were not understood well enough to realistically permit an attempt at gene therapy for these diseases. These difficulties spurred research on alternative approaches which has unexpectedly led to the development of techniques to use gene therapy for the treatment of both rare genetic disorders as well as more common "nongenetic" diseases such as cancer. Our research has focused on one of the most promising cellular alternatives to the bone marrow stem cell, the T lymphocyte. This paper summarizes the historical background and evolution of thinking which led to the initial clinical applications of gene transfer and gene therapy in man.
Blaese
R M
RM
Cellular Immunology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
D000243:Adenosine Deaminase / Q000172:deficiency; D001853:Bone Marrow; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D013601:T-Lymphocytes; D014162:Transfection
D000243:Adenosine Deaminase