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Design and In Vitro Use of Antisense Oligonucleotides to Correct Pre-mRNA Splicing Defects in Inherited Retinal Dystrophies

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Retinal Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1715))

Abstract

Antisense oligonucleotides (AONs) are small molecules able to bind to the pre-mRNA and modulate splicing. The increasing amount of intronic mutations leading to pseudoexon insertion in genes underlying inherited retinal dystrophies (IRDs) has highlighted the potential of AONs as a therapeutic tool for these disorders. Here we describe how to design and test AON molecules in vitro in order to correct pre-mRNA splicing defects involved in IRDs.

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Acknowledgments

This work was financially supported by the Netherlands Organisation for Scientific Research (NWO) (VENI 916.10.096), the Foundation Fighting Blindness (FFB) USA (TA-GT-0912-0582-RAD), the JANIVO stichting, the Stichting August F. Deutman Researchfonds Oogheelkunde, the Rotterdamse Vereniging Blindenbelangen, the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, the Gelderse Blindenstichting, the Stichting Winckel-Sweep and the Stichting Nederlands Oogheelkundig Onderzoek (all to R.W.J.C.) and 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 A.G. and R.W.J.C. This work was also supported by the Foundation Fighting Blindness USA, grant no. PPA-0517-0717-RAD (to A.G. and R.W.J.C.). The funding organizations had no role in the design or conduct of this research. They provided unrestricted grants.

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Authors and Affiliations

  1. Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands

    Alejandro Garanto & Rob W. J. Collin

Authors
  1. Alejandro Garanto
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  2. Rob W. J. Collin
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Corresponding author

Correspondence to Alejandro Garanto .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

    Camiel J.F. Boon

  2. Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

    Jan Wijnholds

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Garanto, A., Collin, R.W.J. (2018). Design and In Vitro Use of Antisense Oligonucleotides to Correct Pre-mRNA Splicing Defects in Inherited Retinal Dystrophies. In: Boon, C., Wijnholds, J. (eds) Retinal Gene Therapy. Methods in Molecular Biology, vol 1715. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7522-8_5

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  • DOI: https://doi.org/10.1007/978-1-4939-7522-8_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7521-1

  • Online ISBN: 978-1-4939-7522-8

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