AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation

Leber congenital amaurosis (LCA) is a severe hereditary retinal dystrophy responsible for congenital or early-onset blindness. The most common disease-causing mutation (>10%) is located deep in intron 26 of the CEP290 gene (c.2991+1655A>G). It creates a strong splice donor site that leads to i...

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Main Authors:	Xavier Gerard, Isabelle Perrault, Sylvain Hanein, Eduardo Silva, Karine Bigot, Sabine Defoort-Delhemmes, Marlèene Rio, Arnold Munnich, Daniel Scherman, Josseline Kaplan, Antoine Kichler, Jean-Michel Rozet
Format:	Article
Language:	English
Published:	Elsevier 2012-01-01
Series:	Molecular Therapy: Nucleic Acids
Subjects:	antisense oligonucleotide CEP290 ciliogenesis repair LCA splice switching-mediated therapy
Online Access:	http://www.sciencedirect.com/science/article/pii/S2162253116300853

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spelling	doaj-4c6ac99f7bf04c2eb9a5d0e5fd83e9c12020-11-24T22:56:03ZengElsevierMolecular Therapy: Nucleic Acids2162-25312012-01-011C10.1038/mtna.2012.21AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 MutationXavier Gerard0Isabelle Perrault1Sylvain Hanein2Eduardo Silva3Karine Bigot4Sabine Defoort-Delhemmes5Marlèene Rio6Arnold Munnich7Daniel Scherman8Josseline Kaplan9Antoine Kichler10Jean-Michel Rozet11Genethon, Evry, FranceINSERM U781 and Department of Genetics, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, FranceINSERM U781 and Department of Genetics, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, FranceCenter for Hereditary Eye Diseases, Department of Ophthalmology, University Hospital of Coimbra, Coimbra, PortugalCentre d’Exploration et de Ressources Thérapeutiques en Ophtalmologie, CERTO, Paris, FranceService d’Exploration de la Vision et Neuro-Ophtalmologie de l’Hôpital Salengro du CHRU de Lilles, Lilles, FranceINSERM U781 and Department of Genetics, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, FranceINSERM U781 and Department of Genetics, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, FranceCNRS UMR 8151-Inserm U1022, Université Paris Descarte-Sorbonne Paris Cité, Chimie-Paristech, Paris, FranceINSERM U781 and Department of Genetics, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, FranceGenethon, Evry, FranceINSERM U781 and Department of Genetics, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, FranceLeber congenital amaurosis (LCA) is a severe hereditary retinal dystrophy responsible for congenital or early-onset blindness. The most common disease-causing mutation (>10%) is located deep in intron 26 of the CEP290 gene (c.2991+1655A>G). It creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. In the present study, we show that the use of antisense oligonucleotides (AONs) allow an efficient skipping of the mutant cryptic exon and the restoration of ciliation in fibroblasts of affected patients. These data support the feasibility of an AON-mediated exon skipping strategy to correct the aberrant splicing.http://www.sciencedirect.com/science/article/pii/S2162253116300853antisense oligonucleotideCEP290ciliogenesis repairLCAsplice switching-mediated therapy
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Xavier Gerard Isabelle Perrault Sylvain Hanein Eduardo Silva Karine Bigot Sabine Defoort-Delhemmes Marlèene Rio Arnold Munnich Daniel Scherman Josseline Kaplan Antoine Kichler Jean-Michel Rozet
spellingShingle	Xavier Gerard Isabelle Perrault Sylvain Hanein Eduardo Silva Karine Bigot Sabine Defoort-Delhemmes Marlèene Rio Arnold Munnich Daniel Scherman Josseline Kaplan Antoine Kichler Jean-Michel Rozet AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation Molecular Therapy: Nucleic Acids antisense oligonucleotide CEP290 ciliogenesis repair LCA splice switching-mediated therapy
author_facet	Xavier Gerard Isabelle Perrault Sylvain Hanein Eduardo Silva Karine Bigot Sabine Defoort-Delhemmes Marlèene Rio Arnold Munnich Daniel Scherman Josseline Kaplan Antoine Kichler Jean-Michel Rozet
author_sort	Xavier Gerard
title	AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation
title_short	AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation
title_full	AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation
title_fullStr	AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation
title_full_unstemmed	AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation
title_sort	aon-mediated exon skipping restores ciliation in fibroblasts harboring the common leber congenital amaurosis cep290 mutation
publisher	Elsevier
series	Molecular Therapy: Nucleic Acids
issn	2162-2531
publishDate	2012-01-01
description	Leber congenital amaurosis (LCA) is a severe hereditary retinal dystrophy responsible for congenital or early-onset blindness. The most common disease-causing mutation (>10%) is located deep in intron 26 of the CEP290 gene (c.2991+1655A>G). It creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. In the present study, we show that the use of antisense oligonucleotides (AONs) allow an efficient skipping of the mutant cryptic exon and the restoration of ciliation in fibroblasts of affected patients. These data support the feasibility of an AON-mediated exon skipping strategy to correct the aberrant splicing.
topic	antisense oligonucleotide CEP290 ciliogenesis repair LCA splice switching-mediated therapy
url	http://www.sciencedirect.com/science/article/pii/S2162253116300853
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AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation

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