RNA therapeutics in ophthalmology - translation to clinical trials. (April 2021)

• Record Type: Journal Article
• Authors: Gupta, Aanchal; Kafetzis, Konstantinos N.; Tagalakis, Aristides D.; Yu-Wai-Man, Cynthia
• Is Part Of: Experimental eye research. Volume 205(2021)
• Publication Date: 2021-04
• Subjects: siRNA -- Antisense oligonucleotide -- Clinical trial -- Glaucoma -- Macular degeneration -- Inherited retinal disorders; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2021.108482
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: The use of RNA interference technology has proven to inhibit the expression of many target genes involved in the underlying pathogenesis of several diseases affecting various systems. First established in in vitro and later in animal studies, small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapeutics are now entering clinical trials with the potential of clinical translation to patients. Gene-silencing therapies have demonstrated promising responses in ocular disorders, predominantly due to the structure of the eye being a closed and compartmentalised organ. However, although the efficacy of such treatments has been observed in both preclinical studies and clinical trials, there are issues pertaining to the use of these drugs which require more extensive research with regards to the delivery and stability of siRNAs and ASOs. This would improve their use for long-term treatment regimens and alleviate the difficulties experienced by patients with ocular diseases. This review provides a detailed insight into the recent developments and clinical trials that have been conducted for several gene-silencing therapies, including ISTH0036, SYL040012, SYL1001, PF-04523655, Sirna-027, QR-110, QR-1123, QR-421a and IONIS-FB-LRX in glaucoma, dry eye disease, age-related macular degeneration, diabetic macular oedema and various inherited retinal diseases. Our aim is to explore the potential of these drugs whilst evaluating their associated advantages and disadvantages, and to discuss the future translation of RNA therapeutics in ophthalmology. Highlights: siRNA and ASO are two major types of gene therapy, utilising oligonucleotides to target genes associated with specific pathologies. We are in a new era where several gene therapies have reached clinical trials and are showing promising results in patients. The eye presents the distinct advantage of being a closed compartmentalised organ where gene therapy and drug delivery can be achieved. Challenges, such as target specificity, safety and efficacy, need to be overcome before they can become standard of care in ophthalmology.