Gene therapy is a promising strategy for the treatment of monogenic disorders. Non-viral gene delivery systems including lipid-based DNA therapeutics offer the opportunity to deliver an encoding gene sequence specifically to the target tissue and thus enable the expression of therapeutic proteins in diseased cells. Currently, available gene delivery approaches based on DNA are inefficient and require improvements to achieve clinical utility. In this Review, we discuss state-of-the-art lipid-based DNA delivery systems that have been investigated in a preclinical setting. We emphasize factors influencing the delivery and subsequent gene expression in vitro, ex vivo, and in vivo. In addition, we cover aspects of nanoparticle engineering and optimization for DNA therapeutics. Finally, we highlight achievements of lipid-based DNA therapies in clinical trials.
Keywords: DNA; clinical trials; gene therapy; genetic disorders; lipid nanoparticles; nanomedicine; non-viral gene delivery; nucleic acid delivery; transfection.