Pushing the Right Buttons: Improving Efficacy of Therapeutic DNA Vectors

Gene therapy represents a potent therapeutical application for regenerative medicine. So far, viral and nonviral approaches suffer from major drawbacks hindering efficient gene therapeutic applicability: the immunogenicity of viral systems on the one hand, and the low gene transfer efficiency of nonviral systems on the other hand. Therefore, there is a high demand for improvements of therapeutical systems at several levels. This review summarizes different DNA vector modifications to enhance biological efficacy and efficiency of therapeutical vectors, aiming for low toxicity, high specificity, and biological efficacy-the cornerstones for successful translation of gene therapy into the clinic. We aim to provide a step-by-step instruction to optimize their vectors to achieve the desired outcome of gene therapy. Our review provides the means to either construct a potent gene therapeutic vector de novo or to specifically address a bottleneck in the chain of events mandatory for therapeutic success. Although most of the introduced techniques can be translated into different areas, this review primarily addresses improvements for applications in transient gene therapy in the field of tissue engineering.