siRNA-mediated gene silencing for non-alcoholic fatty liver disease: A comprehensive review of molecular targets

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global public health distress, with an estimated 25% of the world population affected. Despite the increasing prevalence and morbidity from, there are currently no approved pharmacological therapies. RNA interference (RNAi) using small interfering RNAs (siRNAs) has emerged as a promising novel strategy for tackling these liver diseases. This review presents a comprehensive overview of the therapeutic potential of siRNAs for NAFLD and non-alcoholic steatohepatitis (NASH), summarizing the key molecular targets that have been investigated using siRNA approaches, including de novo lipogenesis, inflammation, apoptosis, xenobiotic, and hypoxia. The review also covers the delivery strategies used and summarizes the mechanism and modifications in siRNAs. The central theme of the article is to evaluate the preclinical investigations that have surveyed the effects of siRNAs on lipotoxicity, inflammation, apoptosis, and hypoxia and stress response, xenobiotic in in-vivo or in-vitro NAFLD/NASH models. The article discusses the prospects and challenges of developing siRNA therapy for patients with NAFLD. The article concludes by highlighting the potential for siRNA therapy to revolutionize the treatment of NAFLD.NASH, and the need for further research to overcome the current challenges and limitations of this therapy. Overall, this review offers a comprehensive and in-depth account of the current state of research in siRNA-based therapy for NAFLD and NASH and serves as a valuable resource for researchers and clinicians working in this field.