Gene

Genetic enhancement

Biology

Gene delivery

Vectors in gene therapy

DNA sequencing

Computational biology

Genetics

In vivo

Bioinformatics

Ex vivo

Viral vector

Recombinant DNA

ACS Nano

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.

Lipid-Based DNA Therapeutics: Hallmarks of Non-Viral Gene Delivery