Gene therapy for liver diseases: methods, challenges and opportunities

genome copies/kg) achieves sustained therapeutic activity in a subset of HOPE-B trial participants with hemophilia B, and LNP-CRISPR editing of ANGPTL3 (0.5 mg/kg mRNA) produces marked reductions in LDL-C and triglycerides. However, several translational challenges have been identified, including unintended activation of the innate immune system and severe hepatotoxicity following high-dose vector administration. These concerns necessitate rigorous and ongoing safety monitoring. In this review, we summarize major advancements, current challenges, and future perspectives in the field of liver-directed gene therapy. Additionally, we highlight key limitations inherent to existing approaches and discuss potential strategies to overcome these barriers and improve therapeutic outcomes.