RNA therapeutics in ophthalmology - translation to clinical trials

Exp Eye Res. 2021 Apr:205:108482. doi: 10.1016/j.exer.2021.108482. Epub 2021 Feb 3.


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.

Keywords: Antisense oligonucleotide; Clinical trial; Glaucoma; Inherited retinal disorders; Macular degeneration; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clinical Trials as Topic
  • Gene Silencing
  • Genetic Therapy / methods*
  • Glaucoma / therapy*
  • Humans
  • Macular Degeneration / therapy*
  • Macular Edema / therapy*
  • Oligonucleotides, Antisense / therapeutic use*
  • RNA, Small Interfering / therapeutic use*
  • Retinal Diseases / therapy*
  • Translational Research, Biomedical


  • Oligonucleotides, Antisense
  • RNA, Small Interfering