Synthetic materials at the forefront of gene delivery

Abstract

The delivery of nucleic acids with transient activity for genetic engineering is a promising methodology with potential applications in the treatment of diseases ranging from cancer and infectious diseases to heritable disorders. Restoring the expression of a missing protein, correcting defective splicing of transcripts and silencing or modulating the expression of genes are powerful approaches that could have substantial benefits in biological research and medicine. Impressive progress in improving gene delivery has been made in the past decade, and several products have reached the market. However, translating the results of in vitro and preclinical studies into functional therapies is hindered by the suboptimal performance of gene delivery vehicles in capturing, protecting and delivering nucleic acid cargoes safely and efficaciously. Chemistry has a key role in the development of innovative synthetic materials to overcome the challenges of producing next-generation gene delivery therapies and protocols. In this Review, we discuss the latest chemical advances in the production of materials for the delivery of nucleic acids to cells and for gene therapy. Non-viral vehicles for the delivery of nucleic acids have potential applications for the treatment of diseases by, for example, restoring, correcting or silencing the expression of genes. In this Review, the authors discuss the latest developments in synthetic materials used for gene delivery and the challenges that must be overcome to transfer these innovations into the clinic.