Molecular genetics and potential gene therapy.

Contemporary molecular techniques including gene cloning, DNA sequencing, and gene transfer permit precise and comprehensive analysis of genetic disorders. For example, the molecular basis of hemoglobin synthesis disorders (the thalassemias) can now be ascribed to more than 30 different specific mutations. These affect virtually all aspects of gene expression. The more recent capacity to reintroduce cloned genes into mammalian cells in a functional form has raised the prospect of gene therapy, that is, the replacement of an abnormal gene with its normal counterpart or merely the introduction of a normal gene into a cell containing a defective copy. Genetic correction of enzyme-deficiency disorders whose effects are manifest in bone-marrow-derived cells seems most likely to be amenable to "somatic" (as opposed to germ line) gene therapy. Treatment of severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency may be a suitable model for this approach. This report will review the molecular genetics of ADA, the methods by which ADA gene sequences may be transferred into various cells, and goals for current and future research.