Wang Ting, Yu Tao, Liu Qian, Sung Tzu-Cheng, Higuchi Akon
State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang 325027, China.
Department of Chemical and Materials Engineering, National Central University, No. 300, Jhongda RD, Jhongli, Taoyuan 32001, Taiwan.
Mol Ther Nucleic Acids. 2024 Jun 3;35(3):102236. doi: 10.1016/j.omtn.2024.102236. eCollection 2024 Sep 10.
Millions of people worldwide have hereditary genetic disorders, trauma, infectious diseases, or cancer of the eyes, and many of these eye diseases lead to irreversible blindness, which is a major public health burden. The eye is a relatively small and immune-privileged organ. The use of nucleic acid-based drugs to manipulate malfunctioning genes that target the root of ocular diseases is regarded as a therapeutic approach with great promise. However, there are still some challenges for utilizing nucleic acid therapeutics because of certain unfavorable characteristics, such as instability, biological carrier-dependent cellular uptake, short pharmacokinetic profiles (RNA), and on-target and off-target side effects (DNA). The development of lipid nanoparticles (LNPs) as gene vehicles is revolutionary progress that has contributed the clinical application of nucleic acid therapeutics. LNPs have the capability to entrap and transport various genetic materials such as small interfering RNA, mRNA, DNA, and gene editing complexes. This opens up avenues for addressing ocular diseases through the suppression of pathogenic genes, the expression of therapeutic proteins, or the correction of genetic defects. Here, we delve into the cutting-edge LNP technology for ocular gene therapy, encompassing formulation designs, preclinical development, and clinical translation.
全球数以百万计的人患有遗传性遗传疾病、创伤、传染病或眼部癌症，其中许多眼部疾病会导致不可逆转的失明，这是一项重大的公共卫生负担。眼睛是一个相对较小且具有免疫豁免权的器官。使用基于核酸的药物来操纵针对眼部疾病根源的功能失常基因，被视为一种极具前景的治疗方法。然而，由于某些不利特性，如不稳定性、依赖生物载体的细胞摄取、较短的药代动力学特征（RNA）以及靶向和脱靶副作用（DNA），利用核酸疗法仍存在一些挑战。脂质纳米颗粒（LNP）作为基因载体的发展是一项革命性进展，推动了核酸疗法的临床应用。LNP有能力包裹和运输各种遗传物质，如小干扰RNA、mRNA、DNA和基因编辑复合物。这为通过抑制致病基因、表达治疗性蛋白质或纠正基因缺陷来解决眼部疾病开辟了途径。在此，我们深入探讨用于眼部基因治疗的前沿LNP技术，包括制剂设计、临床前开发和临床转化。
