Applications of antisense oligonucleotides for the treatment of inherited retinal diseases.
OBJECTIVE
Over the last years, antisense oligonucleotides (AONs) have gained attention as a therapeutic tool for the treatment of ocular diseases such as cytomegalovirus retinitis, keratitis-induced corneal neovascularization, and inherited retinal diseases (IRDs). In this review, we summarize the recent key findings, and describe the challenges and opportunities that lie ahead to translate AON-based therapies to the clinic, in particular for IRDs.


RESULTS
The efficacy of AONs to restore splice defects and cellular phenotypes associated with a common mutation in CEP290 was demonstrated in patient-derived optic cups and in a transgenic mouse model, respectively. In addition, allele-specific knockdown of a mutant RHO allele resulted in a delay of photoreceptor cell death and functional preservation of these cells in a transgenic rat model.


CONCLUSIONS
As demonstrated by several preclinical efficacy studies, AON-based therapy is moving to the clinic for the treatment of some genetic subtypes of IRD. More insights into the delivery of these molecules, the duration of the therapeutic effect, and potential off-target effects will be essential to further shape the transition to the clinic and reveal the true potential of AON-based therapy for retinal diseases.
aDepartment of Human Genetics bDonders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Rob W J
RW
Collin
Alejandro
A
Garanto
D000818:Animals; D004195:Disease Models, Animal; D005091:Exons; D015316:Genetic Therapy; D006801:Humans; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics / Q000628:therapy*
D016376:Oligonucleotides, Antisense