Bioinspired and Biomimetic Gene Delivery Systems

Gene therapy that can introduce, counteract, or replace genes possesses great potential to address diseases at their genetic roots. A wide range of technologies, such as RNA interference, genome editing, DNA transformation, and mRNA vaccines, have been extensively investigated to modulate gene expression in an attempt to treat a myriad of diseases. Despite the great promise of gene therapeutics, a series of intracellular and extracellular barriers must be surmounted, including rapid clearance in circulation, insufficient site-specific accumulation, suboptimal cellular internalization, and deficient transfection efficiency. Advances in the delivery systems for gene delivery bring about profound progress in enhancing the bioavailability and biocompatibility of gene therapeutics. Notably, bioinspired and biomimetic gene delivery systems have emerged, which draw inspiration from natural processes and recapitulate the desired traits and functions of viruses, bacteria, exosomes, and eukaryotic cells. The integration of bioinspired and biomimetic designs can overcome biological barriers, improve the pharmacokinetic profile, and efficiently transport gene therapeutics to target cells. As such, these platforms amplify the therapeutic efficacy and reduce side effects, thus expediting the clinical translation of gene therapy. Herein, we summarize the latest advances in designing bioinspired or biomimetic delivery systems, introduce their advantages, and discuss the obstacles to overcome with rational designs.