A gene delivery vehicle is proposed that uses unique features of viral proteins in a targeted, nonviral gene delivery system. The key features of this system that will lend themselves to gene therapy are (1) the missile-like targeting capacity; (2) the capacity to transport DNA, and, therefore, therapeutic genes; (3) the lack of size restriction and, therefore, the potential capacity to carry any size gene; (4) the lack of viral genes and, therefore, virulence; (5) the enhanced ability to enter cells and deliver therapeutic genes. The system is expected to retain some of the best properties of viral vectors while taking advantage of mechanisms that viruses have evolved to efficiently enter cells. This system is expected to improve these mechanisms by introducing cell type-specific targeting capabilities. Because the system is nonviral in nature, it avoids problems inherent in biologic agents, thus enabling pharmaceutical quality control over the final preparations. Potential application of this system includes targeted delivery of therapeutic genes or drugs for cancer treatment or gene replacement therapy. The model system uses heregulin as a targeting ligand for breast cancer, and herpes simplex thymidine kinase as the therapeutic gene.
