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Chronic liver diseases are a rapidly growing threat to global health, causing approximately 2 million deaths annually—half from complications of cirrhosis and half from viral hepatitis and hepatocellular carcinoma. 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’s unique anatomical and physiological characteristics. We overview the liver physiology and function, and the underlying mechanisms of gene therapy—including 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. By addressing the current challenges and opportunities, this review underscores the transformative potential of nanoengineered gene therapeutics in advancing liver disease treatment and shaping the future of precision hepatology.
Kozlov et al. (Mon,) studied this question.