Targeted Gene Delivery by Virosomes*

In 1990, the first federally approved clinical trials for treatment of a genetic disorder by gene therapy began under the leadership of R. Michael Blease, W. French Anderson, and their colleagues at the National Institutes of Health. This technique involves the identification of required DNA sequences and cell types followed by appropriate ways of DNA delivery to the diseased cells. The therapeutic potential ranges from treating of genetic defects and slowing the progression of tumors to fighting viral infections and curing neurodegenerative disorders. A unique set of problems, such as the lack of eff cient delivery systems, lack of sustained expression, and host immune reactions still put forward formidable challenges. It has been almost unanimously pointed out that the major constraint in the field of gene therapy is to devise ideal “vehicles” to target appropriate cells and achieve physiological levels of the desired gene product (1 ). Several new strategies have been presented in the recent past for correction of genetic diseases of muscle and skin. Encouraging reports have been published in delivering genes encoding liver-derived factor IX to correct hemophilia B and fumarylacetoacetate hydrolase to cure hereditary tyrosinemia type I. Serious attempts to target genes to precise locations (such as airway epithelial cells of the respiratory tract) in diseases such as cystic fibrosis have so far proved to be difficult and exemplify the need for new delivery methods. Newer viral and nonviral vectors/vehicles, which hold promise to facilitate target-specific vector uptake and retention and are able to evade unwanted immune responses, constitute the major demanding criteria for durable and successful gene therapy for genetic diseases (2 ).