全世界数百万人患有遗传性遗传病,创伤,传染病,或者眼睛的癌症,许多眼病会导致不可逆转的失明,这是一个重大的公共卫生负担。眼睛是一个相对较小的免疫特权器官。使用基于核酸的药物来操纵靶向眼部疾病根源的功能不良的基因被认为是具有巨大前景的治疗方法。然而,由于某些不利的特征,在体内利用核酸疗法仍然存在一些挑战,比如不稳定,生物载体依赖性细胞摄取,体内短药代动力学曲线(RNA),以及中靶和脱靶副作用(DNA)。脂质纳米颗粒(LNP)作为基因载体的开发是革命性的进步,为核酸疗法的临床应用做出了贡献。LNP具有捕获和转运各种遗传物质的能力,如小干扰RNA,mRNADNA,和基因编辑复合物。这为通过抑制致病基因来解决眼部疾病开辟了途径,治疗性蛋白质的表达,或纠正遗传缺陷。这里,我们深入研究了眼科基因治疗的尖端LNP技术,涵盖配方设计,临床前发展,和临床翻译。
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 in vivo because of certain unfavorable characteristics, such as instability, biological carrier-dependent cellular uptake, short pharmacokinetic profiles in vivo (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.