ABSTRACT

Introduction

In the retina, noncoding RNA (ncRNA) plays an integral role in regulating apoptosis, inflammatory responses, visual perception, and photo-transduction, with altered levels reported in diseased states.

Areas covered

MicroRNA (miRNA), a class of ncRNA, regulates post-transcription gene expression through the binding of complementary sites of target messenger RNA (mRNA) with resulting translational repression. Small-interfering RNA (siRNA) is a double-stranded RNA (dsRNA) that regulates gene expression, leading to selective silencing of genes through a process called RNA interference (RNAi). Another form of RNAi involves short hairpin RNA (shRNA). In age-related macular degeneration (AMD) and diabetic retinopathy (DR), miRNA has been implicated in the regulation of angiogenesis, oxidative stress, immune response, and inflammation.

Expert opinion

Many RNA-based therapies in development are conveniently administered intravitreally, with the potential for pan-retinal effect. The majority of these RNA therapeutics are synthetic ncRNA’s and hold promise for the treatment of AMD, DR, and inherited retinal diseases (IRDs). These RNA-based therapies include siRNA therapy with its high specificity, shRNA to ‘knock down’ autosomal dominant toxic gain of function-mutated genes, antisense oligonucleotides (ASOs), which can restore splicing defects, and translational read-through inducing drugs (TRIDs) to increase expression of full-length protein from genes with premature stop codons.

中文翻译：

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视网膜疾病的 RNA 疗法

摘要

介绍

在视网膜中，非编码 RNA (ncRNA) 在调节细胞凋亡、炎症反应、视觉感知和光转导中发挥着不可或缺的作用，据报道在患病状态下其水平发生了变化。

涵盖的领域

MicroRNA (miRNA) 是一类 ncRNA，通过与靶信使 RNA (mRNA) 的互补位点结合并产生翻译抑制来调节转录后基因表达。小干扰 RNA (siRNA) 是一种双链 RNA (dsRNA)，可调节基因表达，通过称为 RNA 干扰 (RNAi) 的过程导致基因选择性沉默。另一种形式的 RNAi 涉及短发夹 RNA (shRNA)。在年龄相关性黄斑变性 (AMD) 和糖尿病视网膜病变 (DR) 中，miRNA 与血管生成、氧化应激、免疫反应和炎症的调节有关。

专家意见

许多正在开发的基于 RNA 的疗法可以方便地在玻璃体内给药，具有泛视网膜效应的潜力。这些 RNA 疗法中的大多数是合成的 ncRNA，有望用于治疗 AMD、DR 和遗传性视网膜疾病 (IRD)。这些基于 RNA 的疗法包括具有高特异性的 siRNA 疗法、“敲低”功能突变基因的常染色体显性毒性增益的 shRNA、可以恢复剪接缺陷的反义寡核苷酸 (ASO) 和翻译通读诱导药物 (TRID) ) 以增加来自具有过早终止密码子的基因的全长蛋白质的表达。