Strategies for overcoming extracellular and intracellular delivery barriers in Liver-Targeted gene therapy

Liver-targeted gene therapy holds great potential for treating diverse hepatic disorders, yet its efficacy is significantly hindered by complex extracellular and intracellular delivery barriers. This review systematically delineates the pathophysiological obstacles that impede the efficient delivery of nucleic acid drugs, spanning from systemic clearance and tissue penetration to cellular uptake and intracellular trafficking. A particular focus is placed on recent advances in engineered non-viral delivery systems designed to prolong systemic circulation and achieve disease-relevant cell-specific targeting, as well as innovative methods to enhance tissue permeation, facilitate cell membrane crossing, and ensure efficient endosomal escape with subsequent subcellular localization. Furthermore, the therapeutic application of these platforms for both monogenic and complex liver diseases is critically evaluated, with attention to their potential and persistent bottlenecks in clinical applications. Integrating insights into barrier biology with rational nanomaterial design would facilitate the development of next‑generation non‑viral gene therapies for precise and effective treatment of hepatic disorders.

Abstract from PubMed (PMID 43009105). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.