FROM GENES TO GENE MEDICINES - RECENT ADVANCES IN NONVIRAL GENE DELIVERY

Over the last decade, research in somatic gene therapy has focused on selected approaches to deliver therapeutic genes to cells both ex vivo and in vivo. While most current gene therapy clinical trials are base d on cell-and viral-mediated approaches, nonviral gene medicines are e merging as potentially safe and effective in the treatment of a wide v ariety of genetic and acquired diseases. Nonviral technologies consist of plasmid-based expression systems containing a gene encoding a ther apeutic protein and synthetic gene delivery systems. In addition to th e therapeutic gene, plasmid-based expression systems contain other gen etic sequences to control the in vivo production and secretion of a pr otein. They may include elements that prolong extrachromosomal gene ex pression, cell-specific promoters and, optionally, gene switches for e nabling drug-regulated gene therapy. Unique gene delivery systems will be required depending upon the biology and (patho)physiology of the t arget tissue. This review provides a critical view of gene therapy wit h a major focus on advanced nonviral technologies to control the in vi vo location and function of administered genes.