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Antisense Oligonucleotide Therapy for Inherited Retinal Dystrophies

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 854))

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.

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Author information

Authors and Affiliations

  1. Laboratory of Genetics in Ophthalmology, INSERM UMR1163-Imagine Institute, Paris Descartes - Sorbonne Paris Cité University, 24 boulevard du Montparnasse, Paris, France

    Xavier Gerard PhD & Jean-Michel Rozet PhD

  2. Department of Human Genetics, Radboud Institute for Molecular Life Sciences Radboud University Medical Center, Geert Grooteplein 10, Nijmegen, The Netherlands

    Alejandro Garanto PhD

  3. Department of Human Genetics (855), Radboud Institute for Molecular Life Sciences Radboud University Medical Center, Geert Grooteplein 10, 6525, Nijmegen, GA, The Netherlands

    Rob W. J. Collin PhD

Authors
  1. Xavier Gerard PhD
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  2. Alejandro Garanto PhD
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  3. Jean-Michel Rozet PhD
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  4. Rob W. J. Collin PhD
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Corresponding author

Correspondence to Rob W. J. Collin PhD .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

  2. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  3. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  4. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  5. Case Western Reserve University Cleveland Clinic Lerner College of Med, Cleveland, Ohio, USA

    Joe Hollyfield

  6. Univ of Florida Dept of Ophthalmology/Arb R112, Gainesville, Florida, USA

    John Ash

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© 2016 Springer International Publishing Switzerland

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Cite this paper

Gerard, X., Garanto, A., Rozet, JM., Collin, R. (2016). Antisense Oligonucleotide Therapy for Inherited Retinal Dystrophies. In: Bowes Rickman, C., LaVail, M., Anderson, R., Grimm, C., Hollyfield, J., Ash, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 854. Springer, Cham. https://doi.org/10.1007/978-3-319-17121-0_69

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