PHARMACEUTICAL APPROACH TO SOMATIC GENE-THERAPY

The pharmaceutical approach to somatic gene therapy is based on consid eration of a gene as a chemical entity with specific physical, chemica l and colloidal properties. The genes that are required for gene thera py are large molecules (>1 x 10(6) Daltons, >100 nm diameter) with a n et negative charge that prevents diffusion through biological barriers such as an intact endothelium, the plasma membrane or the nuclear mem brane. New methods for gene therapy are based on increasing knowledge of the pathways by which DNA may be internalized into cells and traffi c to the nucleus, pharmaceutical experience with particulate drug deli very systems, and the ability to control gene expression with recombin ed genetic elements. This article reviews two themes in the developmen t of gene therapies: first, the current approaches involving the admin istration of cells, viruses and plasmid DNA; second, the emerging phar maceutical approach to gene therapy based on the pharmaceutical charac teristics of DNA itself and methods for advanced drug delivery.