Pharmaceutical Approach to Somatic Gene Therapy

The pharmaceutical approach to somatic gene therapy is based on consideration of a gene as a chemical entity with specific physical, chemical and colloidal properties. The genes that are required for gene therapy are large molecules (>1 × 106 Daltons, >100 nm diameter) with a net negative charge that prevents diffusion through biological barriers such as an intact endothelium, the plasma membrane or the nuclear membrane. New methods for gene therapy are based on increasing knowledge of the pathways by which DNA may be internalized into cells and traffic to the nucleus, pharmaceutical experience with particulate drug delivery systems, and the ability to control gene expression with recombined genetic elements. This article reviews two themes in the development of gene therapies: first, the current approaches involving the administration of cells, viruses and plasmid DNA; second, the emerging pharmaceutical approach to gene therapy based on the pharmaceutical characteristics of DNA itself and methods for advanced drug delivery.