Gene therapy

The classic use of gene therapy is for correction of diseases due to a single gene defect and hemopoietic stem cell transplantation with genetically modified cells, offers the possibility to treat many congenital disorders where bone marrow transplantation from an allogeneic donor is the only current curative therapy. However, the inefficiency of currently available vectors has delayed such applications of gene therapy, apart from diseases such as ADA deficiency of Gaucher disease where low level expression may produce benefit Gene transfer has in fact been more commonly used over the past few years to answer biological questions about bone marrow transplantation and to develop novel therapies for cancer. Gene marking bas been used to determine if harvested progenitor cells in marrow and blood are contaminated with tumorigenic cells and whether attempts to remove such cells have been successful. In patients with AML, neuroblastoma and CML, it has been shown that residual malignant cells may contribute to relapse after autologous BMT. Double marking techniques are being used to compare reconstitution of two distinct hemopoietic stem cells sources or treatments. Gene transfer is also being used to trace the fate of adoptively transferred immune system cells and to modulate T cell function. For example, transfer of a suicide gene may allow destruction of infused T cells if they cause adverse effects. In patients with cancer, gene transfer has been used to increase immunogenidty of tumor cells, to alter the malignant phenotype by blocking oncogenes or modifying tumor suppressor gene expression, or to alter tumor cells by introducing a gene encoding an enzyme that converts a harmless prodrug into a cytotoxic agent Finally transfer of drug resistance genes to hemopoietic progenitors may enable patients to resist the myelosuppressive effects of cytotoxic drugs and allow more intensive chcmothcraov which mav result in hieher cure rates.