Antisense Oligonucleotide-Based Splice Correction of a Deep-Intronic Mutation in CHM Underlying Choroideremia
SourceAdvances in Experimental Medicine and Biology, 1074, (2018), pp. 83-89
Article / Letter to editor
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Advances in Experimental Medicine and Biology
SubjectRadboudumc 12: Sensory disorders DCMN: Donders Center for Medical Neuroscience
Choroideremia is a progressive genetic eye disorder caused by mutations in the CHM gene that encodes the Rab escort protein-1 (REP-1). One of the many CHM mutations described so far is a deep-intronic variant, c.315-4587T>A, that creates a novel splice acceptor site resulting in the insertion of a 98-bp pseudoexon in the CHM transcript. Antisense oligonucleotides (AONs) are a potential therapeutic tool for correcting splice defects, as they have the properties to bind to the pre-mRNA and redirect the splicing process. Previously, we used AONs to correct aberrant splicing events caused by a recurrent intronic mutation in CEP290 underlying Leber congenital amaurosis. Here, we expand the use of these therapeutic molecules for the c.315-4587T>A deep-intronic mutation in CHM by demonstrating splice correction in patient-derived lymphoblast cells.
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