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 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.
1] Genethon, Evry, France [2] CNRS UMR 8151-Inserm U1022, Université Paris Descarte-Sorbonne Paris Cité, Chimie-Paristech, Paris, France.
Xavier
X
Gerard
Isabelle
I
Perrault
Sylvain
S
Hanein
Eduardo
E
Silva
Karine
K
Bigot
Sabine
S
Defoort-Delhemmes
Marlèene
M
Rio
Arnold
A
Munnich
Daniel
D
Scherman
Josseline
J
Kaplan
Antoine
A
Kichler
Jean-Michel
JM
Rozet