Advances in Hydrogel-Mediated Gene Therapy in Ophthalmology: Future Directions and Therapeutic Potential

Abstract Hydrogel-mediated gene therapy has achieved significant progress in the field of ophthalmology in recent years. As three-dimensional polymeric networks with high water content, hydrogels exhibit excellent biocompatibility, localized targeting capability, and sustained-release properties. These characteristics make them ideal carriers for nucleic acid-based drugs, including DNA, RNA, and gene editing systems. They can significantly improve the therapeutic efficacy and delivery kinetics of ocular drug administration, demonstrating unique advantages in the special ocular environment. This review systematically examines the current state of hydrogel-based gene therapy research in ophthalmology. First, recent advances in gene therapy are summarized, and the involved gene types and technical strategies are categorized. Second, various categories of hydrogels are outlined, including photo-responsive, temperature-sensitive, and pH-responsive hydrogels. Their key characteristics for ocular gene delivery are also summarized. Furthermore, this article focuses on analyzing the design strategies for hydrogel-mediated gene therapy. Key design considerations include gene encapsulation, stability control, and release kinetics. In addition, various gene-hydrogel integration strategies, including covalent conjugation and physical loading methods. Their impacts on transfection efficiency and therapeutic outcomes are also analyzed. Additionally, cutting-edge applications of hydrogel-based gene therapy in treating ocular diseases are systematically introduced, covering both anterior segment and fundus diseases. Finally, the limitations and future development prospects of these gene therapy hydrogel systems in ophthalmic research are discussed.