The prospects of DNA based therapeutics is increasing daily for both genetic diseases (e.g. cystic fibrosis, and muscular dystrophy) and for acquired diseases (i.e., cancer). Currently, over 200 patients are enrolled in Phase I studies in the U.S. (Primarily for cancer). However, there are still many shortcomings in the currently employed gene delivery systems. The objectives of this project are to provide an improved delivery system for gene therapy. Artificial viral envelopes (AVE) are an innovative delivery system which combines the low immunogenicity of anionic liposomes with some of the targeting and membrane fusogenic properties of envelope viruses. The use of synthetic peptides to compress and target transgenic DNA is novel approach toward enhanced gene delivery. The effectiveness of this approach will be determined by evaluating the encapsulation of efficiency of labeled plasmid DNA using both a fluorescent augmented cell sorting and radiolabeling followed by scintillation counting. Transgene expression will be determined for two different reporter genes, chloramphenicol acetyltransferase (CAT) and placental alkaline phosphatase (PAP). This will provide both a quantitative (activity/mg protein/h) measurement (CAT) and a more qualitative evaluation, number of cells positive by histochemical analysis (PAP).Proposed commercial application:The commercial application of gene therapy is enormous. PulmozymeTM is an 80 million dollar a year product, which is only 20% effective in treating the symptoms of cystic fibrosis. The market for an effective cure for this disease alone may be as much as 10 times this amount.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
