NONVIRAL GENE DELIVERY SYSTEMS

One of the central challenges in gene therapy is to find safe vectors capable of transporting genes efficiently into the target cells. There fore a suitable DNA carrier must be designed to allow subsequent expre ssion of the gene at a therapeutic level and, if possible, restricted to the organ to be treated or to produce the transgene. Encouraging re sults both in animals and humans have been obtained using viruses. How ever, safety concerns about viral vectors have led researchers to deve lop parallel non-viral systems. These systems include liposomes, catio nic lipids, targeted and peptide-based systems, and polymers, as well as direct injection of plasmid DNA into tissues. Although expression o f foreign genes has been obtained in animals after Systemic administra tion of DNA/carrier complexes, kinetics and sites of expression still cannot be controlled after intravenous injection. Therefore, non-viral systems are mainly used by local route and promising results have bee n obtained in different animal models. Human clinical trials using cat ionic lipids are now underway in cystic fibrosis and cancer and prelim inary data have demonstrated the feasibility as well as the safety of this type of approach. However, therapeutic effects have yet to be dem onstrated. The design of efficient non-viral systems for gene therapy will require a better understanding of their physicochemistry and the mechanism by which they deliver DNA into the cell.