Clínica Universidad de Navarra, Pamplona, Spain.
Sylentis, Madrid, Spain.
Methods Mol Biol. 2021;2282:417-442. doi: 10.1007/978-1-0716-1298-9_23.
The field of RNAi therapeutics has quickly adapted to the treatment of ocular diseases. Although the eye provides a unique system for the delivery of siRNAs, its complex structure and composition fostered the development of novel strategies for efficient gene silencing in the target compartment. Moreover, anterior and posterior segments differ in their multiple drug barriers and clearance mechanisms. This chapter summarizes the recent achievements in terms of routes of administration, chemical modifications, and delivery systems for siRNAs that specifically apply to eye disorders. Methods employed for siRNA detection/quantitation in ocular tissues are also described, together with safety concerns that need to be addressed to fulfill regulatory requirements of new drug approval. Even though RNAi therapies for ocular diseases have not yet translated into patient care, we document herein the rising number of candidate drugs currently under preclinical or clinical development.
RNAi 治疗学领域已迅速适应眼部疾病的治疗。尽管眼睛为 siRNA 的递供提供了独特的系统，但它的复杂结构和组成促进了新型策略的发展，以实现靶位中有效基因沉默。此外，前节和后节在多种药物屏障和清除机制方面存在差异。本章总结了在适用于眼部疾病的给药途径、化学修饰和 siRNA 传递系统方面的最新进展。还描述了用于眼部组织中 siRNA 检测/定量的方法，以及需要解决以满足新药批准的监管要求的安全性问题。尽管眼部疾病的 RNAi 疗法尚未转化为患者护理，但本文记录了当前处于临床前或临床开发阶段的候选药物数量不断增加。
