Current advances in non-viral gene delivery systems: Liposomes versus extracellular vesicles

In the past decade, nucleic acid-based drugs have emerged as an extremely promising approach for silencing specific disease-related genes and targeting undruggable ones. However, most nucleic acid drug therapies have not advanced to clinical practice due to their poor stability against serum enzyme degradation and cytotoxicity. Nanoscale drug delivery vehicles show potential to improve efficacy of nucleic acid drugs via targeted delivery to disease-causing genes, yet, safe and efficient nanocarriers remain elusive. Lipid-based nanoparticles such as liposomes (LSs) and extracellular vesicles (EVs) are among the most extensively exploited nanoscale vehicles for therapeutic cargo delivery. LS-based nucleic acid therapies have been used for several years, with many already adopted to the clinic. More recently, EVs hold considerable promise as nucleic acid delivery vehicles due to their high biocompatibility, low immunogenicity, and the inherent abilities to interact with target cells and cross biological barriers. Moreover, a novel LS/EV hybrid gene delivery system has been engineered to preserve the benefits of both systems and generate an advanced drug delivery system. The current review focuses specifically on LS- and EV-based gene therapies and provides the key advantages and shortcomings of these systems with particular emphasis on their potential use as therapeutic vectors.