Nucleic acid therapeutics for liver diseases: A decade of technological convergence and clinical challenges

This review synthesizes a decade of advancements in nucleic acid therapeutics for liver diseases, incorporating bibliometric analysis and translational evaluation. The field has evolved from foundational viral vector engineering to precision genome editing and RNA-based modulation, with advancements in CRISPR-Cas9 and innovations in non-viral delivery systems. Our analysis highlights the concentrated research efforts made in metabolic disorders and hepatocellular carcinoma, and reveals an emerging emphasis on multifactorial pathologies. Although clinical milestones highlight important advancements in targeting strategies, significant challenges remain in immune compatibility and preclinical translation. The integration of computational modeling, human-relevant disease models, and combinatorial strategies places nucleic acid therapies in a unique position to tackle the evolving global liver disease burden through mechanism-driven interventions.