Embodiments of the present invention are generally related to a method of enhancing the transfection efficiency and immunological/pharmacological/therapeutic responses of concurrent gene-based vaccinations or therapies delivered by a wide range of non-viral particles, viral vectors or viral-biomaterials hybrid particles. In particular, embodiments of the present invention are directed to a method of electroporation which enhances the transfection efficiency of RNA replicon loaded lipid-based nanoparticles in-vivo as well as greatly improves immunogen-specific immune responses of such RNA-based vaccinations. This invention also applies to other gene-based vaccination and therapy using non-viral particles, viral based vectors or viral-biomaterials hybrid particles, in conjunction with the said electroporation regimen.