Genetic medicine is offering hope as new
therapies are emerging for many previously untreatable diseases. The eye is at the forefront of these advances, as exemplified by the approval of Luxturna® by the United States Food and Drug Administration (US FDA) in 2017 for the treatment of one form of
Leber Congenital Amaurosis (LCA), an inherited
blindness. Luxturna® was also the first in vivo human gene therapy to gain US FDA approval. Numerous gene therapy clinical trials are ongoing for other
eye diseases, and novel delivery systems, discovery of new drug targets and emerging technologies are currently driving the field forward. Targeting
RNA, in particular, is an attractive therapeutic strategy for
genetic disease that may have safety advantages over alternative approaches by avoiding permanent changes in the genome. In this regard,
antisense oligonucleotides (ASO) and RNA interference (RNAi) are the currently popular strategies for developing
RNA-targeted
therapeutics. Enthusiasm has been further fuelled by the emergence of clustered regularly interspersed short palindromic repeats (CRISPR)-CRISPR associated (Cas) systems that allow targeted manipulation of
nucleic acids.
RNA-targeting CRISPR-Cas systems now provide a novel way to develop
RNA-targeted
therapeutics and may provide superior efficiency and specificity to existing technologies. In addition,
RNA base editing technologies using CRISPR-Cas and other modalities also enable precise alteration of single
nucleotides. In this review, we showcase advances made by
RNA-targeting systems for ocular disease, discuss applications of ASO and RNAi technologies, highlight emerging CRISPR-Cas systems and consider the implications of
RNA-targeting
therapeutics in the development of future drugs to treat
eye disease.