The research program we propose will consist of four projects, each focused on the use of gene therapy to treat human genetic diseases resulting from specific enzyme deficiencies. The genetic diseases which will be investigated include: 1) Urea cycle enzyme deficiencies, 2) The Lesch-Nyhan Syndrome, 3) Severe combined immunodeficiency disease, and 4) Phenylketonuria. The projects include liver specific enzymes, a lymphocyte specific enzyme, and an enzyme with increased expression in central nervous system tissue. Freely diffusable metabolites are believed to be associated with each enzyme deficiency, making bone marrow an obvious choice for gene transfer. However, efforts at gene transfer into hepactocytes will also be attempted in the two projects involving liver specific enzymes. The laboratories involved in each research project have already obtained full length copies of the relevant cDNAs and have constructed functional minigenes capable of expression following gene transfer into cultured cells. In most cases the minigenes have been placed in helper free preparations of defective retroviruses that are capable of highly efficient gene transfer. Thus, our studies are now focused on the use of animal models as a prelude to human clinical trials. The long term goal of this work is to develop methods for treating human genetic diseases by gene therapy.
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| Ledley, F D (1987) Somatic gene therapy for human disease: background and prospects. Part II. J Pediatr 110:167-74 |
| Ledley, F D; Hahn, T; Woo, S L (1987) Selection for phenylalanine hydroxylase activity in cells transformed with recombinant retroviruses. Somat Cell Mol Genet 13:145-54 |
| Ledley, F D (1987) Somatic gene therapy for human disease: background and prospects. Part I. J Pediatr 110:1-8 |
