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Despite this, effective diagnostic and therapeutic options remain limited, prompting an urgent need for novel translational strategies. Gene-based therapeutics have emerged as a promising solution compared to conventional treatments. This review highlights the therapeutic potential of delivering nucleic acid drugs using nanoengineered materials, which take advantage of the liver\u2019s unique anatomical and physiological characteristics. We overview the liver physiology and function, and the underlying mechanisms of gene therapy\u2014including gene augmentation, gene silencing, and gene editing. Special attention is given to current strategies and mechanisms of gene therapy. Furthermore, we discuss the clinical translation, benefits, and limitations of gene-based approaches in treating the most widespread liver diseases and pathologies such as nonalcoholic fatty liver disease, hepatic inflammation, hepatitis, and fibrosis. 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