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Review
. 2021 May;21(5):603-613.
doi: 10.1080/14712598.2021.1856365. Epub 2020 Dec 16.

RNA therapeutics for retinal diseases

Michael C Gemayel  1 , Ashay D Bhatwadekar  1 , Thomas Ciulla  1   2   3
Affiliations
Review

RNA therapeutics for retinal diseases

Michael C Gemayel et al. Expert Opin Biol Ther. 2021 May.

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.

Keywords: Antisense oligonucleotides; RNA therapeutics; inherited retinal disease; microRNA; noncoding RNA; short hairpin RNA; small-interfering RNA; translational read-through inducing drugs.

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Conflict of interest statement

Declaration of Interests

TA Ciulla has an employment relationship at Clearside Biomedical Inc. However, this manuscript was written during his work as a Volunteer Clinical Professor of Ophthalmology at Indiana University School of Medicine, and none of the work herein represents any official position or opinion of Clearside or its management. A Bhatwadekar reports funding support from NEI R01 EY027779. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1:
Figure 1:
mRNA Translation at Ribosome Source: https://commons.wikimedia.org/wiki/File:Ribosome_mRNA_translation_en.svg
Figure 2:
Figure 2:
Pre-mRNA and mRNA. From Nastypatty / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0), https://commons.wikimedia.org/wiki/File:Pre-mRNA.svg.
Figure 3.
Figure 3.
Delivery of shRNA and the mechanism of RNA interference. From: Dan Cojocari / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0), https://commons.wikimedia.org/wiki/File:ShRNA_Lentivirus.svg
Figure 4:
Figure 4:
Antisense DNA oligonucleotide. Source: https://commons.wikimedia.org/wiki/File:Antisense_DNA_oligonucleotide.png
See this image and copyright information in PMC

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