We will describe hybrid vectors comprising electrostatic complexes of “bald” retrovirus- and lentivirus-like particles (VLPs) – lacking the viral Env protein – and cationic lipids or polymers. We hypothesize that the RVLP/polycation complexes are taken up by cells via endocytic processes, the synthetic component mediates escape into the cytoplasm, and the virus components provide efficient trafficking of the genes to the nucleus. In addition, targeting ligands are attached to the synthetic component to direct cell-specific delivery. We will report investigation of the effects of vector composition, especially alternate polycations, on gene delivery activity and demonstrate targeting of hybrid vectors by conjugation of targeting ligands to the synthetic component of the vector. Early results demonstrate formation of VLP/lipid and VLP/polymer complexes and efficient targeted gene delivery to model cell lines. In addition, because the transgenes are integrated into the cell genome by the virus, VLP/polycation nanovectors result in stable gene expression compared to conventional non-viral vectors. Human gene therapy awaits development of improved vectors that provide safety, specificity and high efficiency. The VLP/polycation nanovectors reported here may represent a novel approach to address this need.