Abstract
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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Acknowledgments
We would like to acknowledge the patients that participated in this study. This work was supported by the following foundations: Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Stichting Blinden-Penning, Landelijke Stichting voor Blinden en Slechtzienden, Stichting Oogfonds Nederland, Stichting MD Fonds, and Stichting Retinal Nederland Fonds that contributed through UitZicht 2015-31, together with the Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting tot Verbetering van het Lot der Blinden, Stichting voor Ooglijders, and Stichting Dowilvo, granted to AG and RWJC. This work was also supported by the Foundation Fighting Blindness USA, grant no. PPA-0517-0717-RAD (to AG, FPMC and RWJC). The funding organizations had no role in the design or conduct of this research. They provided unrestricted grants.
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Garanto, A., van der Velde-Visser, S.D., Cremers, F.P.M., Collin, R.W.J. (2018). Antisense Oligonucleotide-Based Splice Correction of a Deep-Intronic Mutation in CHM Underlying Choroideremia. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_11
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