Optimizing the targeting of lipid nanoparticles for gene therapy

Abstract

Gene drugs based on nucleic acid molecules have shown great potential in the treatment of various diseases. Lipid nanoparticles (LNPs) are currently the most advanced carriers for delivering nucleic acids. However, gene therapy fails to meet the clinical needs of organs other than the liver due to accumulation in the liver. Precise delivery of nucleic acids to specific target organs and target cells has become a key challenge in bringing gene therapy to the clinic. In this review, we present the typical composition and targeting properties of LNPs. Then we systematically describe the strategies and research progress to optimize the targeting properties of LNPs from three perspectives: surface modification, formulation optimization, and novel lipid molecule design. This review will further inspire researchers to rationally design targeted LNPs to advance the development of gene therapy.