Promising RNA-based cancer gene therapy using extracellular vesicles for drug delivery

Introduction: RNA-based cancer gene therapy shows potential in cancer treatment. However, the safe and efficient transfer of therapeutic RNA to target cells has always been a challenge. The ideal drug delivery system should be effective with low immunogenicity and toxicity. Besides, a high specificity of drug delivery is necessary to improve efficacy and avoid the side effects associated with tumor heterogeneity. As endogenous RNA vehicles, extracellular vesicles (EVs) have shown their advantages and potential as drug delivery systems in gene therapy. Areas covered: We summarize the performance of EVs as a drug delivery system in RNA-based cancer gene therapy and discuss the advantages, limitations, and potentials of this translational medicine. In addition, we compare the characteristics and differences of current drug delivery systems and expound the principles of selecting a drug delivery system suitable for cancer gene therapy. Expert opinion: EVs are highly biocompatible membrane structures with low cytotoxicity which provide a new choice for drug delivery in RNA-based cancer gene therapy. The specificity of engineered EVs and artificial EV-mimetics can be improved through peptide or polymer decoration. However, apart from therapeutic RNA, EVs naturally carry many molecules. This may lead to unpredictable effects and thus should be applied with caution.