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Lipid nanoparticle-based delivery of small interfering RNAs: New possibilities in the treatment of diverse diseases
(Pergamon-Elsevier Science Ltd, 2025) Askarizadeh, Anis; Vahdat-Lasemi, Fatemeh; Karav, Sercan; Kesharwani, Prashant; Sahebkar, Amirhossein
RNA interference (RNAi) is a well-known post-transcriptional gene-silencing mechanism that has garnered significant attention as a potentially powerful therapeutic procedure for combating recalcitrant diseases. Small interfering RNA (siRNA) as an effective RNAi tool mediates gene silencing pathway by mRNA degradation in cells and presents a unique strategy for the treatment of rebellious diseases. However, the low stability and suboptimal pharmacokinetic behavior of naked siRNAs have made it necessary to employ a delivery vehicle to protect siRNA against degradation and allow for its intracellular delivery. Among a plethora of available delivery platforms, lipid nanoparticles (LNPs) have received significant research attention and are currently recognized as the most advanced delivery system for RNA-based therapeutic agents. This is exemplified by the approval of Onpattro (R) for treating amyloidosis in the US and the European Union in 2018, as well as the development of COVID-19 mRNA vaccines. This review aims to provide a comprehensive evaluation of the potential effectiveness of lipid-based nanoparticles as a delivery system for siRNA in treating a wide array of diseases.