CELL-TYPE-SPECIFIC AND INDUCIBLE PROMOTERS FOR VECTORS IN GENE-THERAPY AS AN APPROACH FOR CELL TARGETING

Gene therapy is used to correct genetic defects or to deliver new ther apeutic functions to the target cells. Viral vectors are employed main ly as a gene delivery system. A great variety of viral expression syst ems have been developed and assessed for their ability to transfer gen es into somatic cells. In particular, retroviral and adenoviral mediat ed gene transfer have been extensively studied and improved. Preclinic al and clinical studies covering a large range of genetic disorders ar e currently underway to solve basic issues dealing with gene transfer efficiencies, regulation of gene expression, and potential risks of th e use of viral vectors. The majority of clinical gene therapy trials t hat employ viral vectors perform ex vivo gene transfer into target cel ls. The main issue in potential clinical application of gene therapy i s the need for increased gene transfer efficiency and target specifici ty associated with regulated gene expression at therapeutically releva nt levels in vivo. Gene regulatory elements, such as promoters and enh ancers, possess cell type specific activities and can be activated by certain induction factors (e.g., hormones, growth factors, cytokines, cytostatics, irradiation, heat shock) via responsive elements. A contr oled and restricted expression of these genes can be achieved using su ch regulatory elements as internal promoters to drive the expression o f therapeutic genes in viral vector constructs. In addition to high le vel and efficient gene expression, minimizing or excluding inappropria te gene expression in surrounding nontarget cells is of great importan ce for numerous gene therapeutic approaches. This contribution furnish es insight into the field of cell type specific promoter and enhancer systems which have been used for targeted and inducible expression of therapeutic genes in certain genetic disorders, viral infections, and malignancies. We also discuss promoters that represent attractive cand idates for the construction of viral vectors.