GENE-THERAPY TO HUMAN-DISEASES - EX-VIVO AND IN-VIVO STUDIES (REVIEW)

The identification of defective genes associated with a number of huma n disorders (tyrosine hydroxylase for Parkinson's disease, aspartylglu cosaminidase in lysosomal storage disease, CFTR in cystic fibrosis, an d LDL receptor in familial hypercholesterolemia) has promoted the deve lopment of strategies aimed at transferring to the somatic cells of th e patient or of animal models vectors carrying the corrected gene. The obstacles to overcome include targeting the specific cell type or org an (liver for Factors VIII and IX in hemophilia), enhancing entry to c ells into non-lysosomal compartments, nuclear import, percentage of ce lls transduced with the therapeutic gene, sustained expression of the transgene in human tissues, and immunogenicity of the transduced cells expressing the recombinant or viral proteins. Improvements in each si ngle of these steps are likely to enhance enormously the potential of gene transfer for the treatment of human diseases. A number of human d iseases including HIV infections and hypertension are approached by so matic gene transfer. VEGF regulating vascular permeability, growth of endothelial cells and angiogenesis, and TGF-B implicated in wound heal ing and in stimulation in synthesis of extracellular matrix, are poten tial targets for restenosis, atherosclerosis, and cancer.