A Review of Nanoparticle-Mediated Delivery Systems for RNA-Based Therapeutics

RNA-based therapeutics, such as RNA interference (RNAi) and mRNA therapies, have shown significant potential in treating diseases like cancer, genetic disorders, and respiratory conditions. However, an ongoing challenge is the efficient and targeted delivery of RNA to specific cells while minimizing toxicity and off-target effects. This review examines recent advancements in nanoparticle( s) (NPs) delivery systems, with a focus on RNA-coated liposomes, lipid nanoparticles (LNPs), and size- and surface-modifiable NPs, aiming to overcome the challenges associated with RNA delivery. We also explore the impact of specific patents in this field. The relevant information was collected from the scientific literature. We discussed various NP platforms and their applications, such as RNA-coated liposomes for oral cancer treatment, dry powder formulations of mRNA-loaded LNPs for pulmonary delivery, and LNP-mediated siRNA delivery for respiratory infections. We also explore NP optimization strategies, such as lipid tail modifications for RNA cargos like mRNA and CRISPR/Cas9. These NP-based systems have led to advancements in tumor targeting, intracellular delivery, and RNA release, demonstrating their promise in RNA therapeutics. Relevant patents, such as WO2016044478A1, which details the use of AAV vectors for treating MYOC glaucoma with RNAi targeting MYOC; WO2011158933A1, which describes a siRNA-based pharmaceutical composition for renal fibrosis using liposomes with retinol as a targeting agent; and WO2019173787A1, which specifies bacterial-toxin-derived constructs for oral siRNA delivery, further validate the progress in RNA delivery technologies. Despite these advancements, challenges such as targeting efficiency, endosomal escape, stability, immune system interactions, and scalability still remain. Continued innovation in RNA nanotechnology, drawing on insights from recent patents, is crucial for developing more effective and personalized RNA-based therapies.