This project is a collaborative effort between Middlesex Sciences, Inc. (MSI) and Dana Farber Cancer Institute to improve the efficiency of DNA vaccines by developing a targeted, protected DNA delivery system. DNA vaccines have the potential to be a more powerful, and safer alternative vaccination against diseases for which antigen-based vaccines are not satisfactory (eg influenza) as well as for which vaccines presently do not exist (eg HIV). One of the major obstacles to the development of these DNA vaccines is the very low efficiency of delivery of the DNA which leads to low expression of the antigen in the target cells. In this proposal we describe the development of a DNA delivery system in which the DNA is particlized using MSI's microparticle technology, and is joined together with a GPI-anchored protein based targeting system developed by Dr. Robert Finberg at Dana Farber. We expect this particlized, targeted DNA delivery system to result in a significant enhancement in overall expression and hence in effective immunogenicity of DNA vaccines. PROPOSED COMMERCIAL APPLICATION: DNA vaccines have the potential of replacing current protein and protein-polysaccharide conjugate vaccines as the preferred method for vaccination. This proposal describes a system which would be the preferred method for delivery of DNA vaccines