title: Antisense Oligonucleotide Therapy for Inherited Retinal Dystrophies.
abstract: Inherited retinal dystrophies (IRDs) are an extremely heterogeneous group of genetic diseases for which currently no effective treatment strategies exist. Over the last decade, significant progress has been made utilizing gene augmentation therapy for a few genetic subtypes of IRD, although several technical challenges so far prevent a broad clinical application of this approach for other forms of IRD. Many of the mutations leading to these retinal diseases affect pre-mRNA splicing of the mutated genes . Antisense oligonucleotide (AON)-mediated splice modulation appears to be a powerful approach to correct the consequences of such mutations at the pre-mRNA level , as demonstrated by promising results in clinical trials for several inherited disorders like Duchenne muscular dystrophy, hypercholesterolemia and various types of cancer. In this mini-review, we summarize ongoing pre-clinical research on AON-based therapy for a few genetic subtypes of IRD , speculate on other potential therapeutic targets, and discuss the opportunities and challenges that lie ahead to translate splice modulation therapy for retinal disorders to the clinic.
authors.affiliation: Laboratory of Genetics in Ophthalmology, INSERM UMR1163-Imagine Institute, Paris Descartes - Sorbonne Paris Cité University, 24 boulevard du Montparnasse, Paris, France. xavier.gerard@inserm.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Gerard
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences Radboud University Medical Center, Geert Grooteplein 10, Nijmegen, The Netherlands. alex.garantoiglesias@radboudumc.nl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Garanto
authors.affiliation: Laboratory of Genetics in Ophthalmology, INSERM UMR1163-Imagine Institute, Paris Descartes - Sorbonne Paris Cité University, 24 boulevard du Montparnasse, Paris, France. jean-michel.rozet@inserm.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rozet
authors.affiliation: Department of Human Genetics (855), Radboud Institute for Molecular Life Sciences Radboud University Medical Center, Geert Grooteplein 10, 6525, Nijmegen, GA, The Netherlands. rob.collin@radboudumc.nl.
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D058499:Retinal Dystrophies / Q000235:genetics* / Q000628:therapy*; D052416:Targeted Gene Repair / Q000379:methods*
chemical_list: D016376:Oligonucleotides, Antisense; D012322:RNA Precursors
keywords: AON; Antisense oligonucleotides; CEP290; Genetic therapy; Inherited retinal dystrophy; Splice correction; Splicing