The following is a summary of the “RNA-targeting strategies as a platform for ocular gene therapy,” published in the January 2023 issue of Progress in retinal and eye research by Kumar, et al.

Genetic medicine is a source of optimism as treatments for many diseases that were once incurable become available. Luxturna®, a drug approved in 2017 by the US FDA to treat one form of Leber Congenital Amaurosis (LCA), an inherited form of blindness, is a prime example of how the eye is at the forefront of these developments. Additionally, Luxturna® was the first in vivo human gene therapy approved by the US Food and Drug Administration. 

There are currently many gene therapy clinical trials being conducted for other ocular diseases, with novel delivery systems, the discovery of new drug targets, and emerging technologies all pushing the field forward. As it does not involve any permanent changes to the genome, targeting RNA is an appealing therapeutic strategy for genetic disease. The most common approaches to creating RNA-targeted therapeutics are antisense oligonucleotides (ASO) and RNA interference (RNAi). 

The development of clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated (Cas) systems, which enable specific manipulation of nucleic acids, has stoked even more interest. RNA-targeting CRISPR-Cas systems offer a new approach to the development of RNA-targeted therapeutics, and they have the potential to be more efficient and specific than current methods. Single nucleotide changes can also be made with pinpoint accuracy thanks to RNA-base editing technologies like CRISPR-Cas. Here, we highlight the progress made by RNA-targeting systems in the treatment of ocular diseases, discuss their applications, highlight new CRISPR-Cas systems, and think about the implications of RNA-targeting therapeutics for the future of drug discovery.

Source: sciencedirect.com/science/article/abs/pii/S1350946222000702