A protein domain-oriented approach to expand the opportunities of therapeutic exon skipping for -associated retinitis pigmentosa.

Loss-of-function mutations in are among the most common causes of syndromic and non-syndromic retinitis pigmentosa (RP). We previously presented skipping of exon 13 as a promising treatment paradigm for -associated RP. However, RP-associated mutations are often private, and evenly distributed along the gene.

Affinity purification of in vivo assembled whirlin-associated protein complexes from the zebrafish retina.

Mutations in WHRN lead to Usher syndrome type 2d or to non-syndromic hearing impairment. The WHRN-encoded gene product whirlin directly interacts with the intracellular regions of the other two Usher syndrome type 2-associated proteins, usherin and ADGRV1. In photoreceptor cells, this protein complex constitutes fibrous links between the periciliary membrane and the connecting cilium.

Generation of Humanized Zebrafish Models for the In Vivo Assessment of Antisense Oligonucleotide-Based Splice Modulation Therapies.

Antisense oligonucleotide (AON)-based splice modulation is the most widely used therapeutic approach to redirect precursor messenger RNA (pre-mRNA) splicing. To study the functional effect of human mutations affecting pre-mRNA splicing for which AON-based splice redirection would be a potential therapeutic option, humanized knock-in animal models are pivotal. A major limitation of using humanized animal models for this purpose is the reported poor recognition of human splice sites by the splicing machineries of other species.

Zebrafish as a Model to Evaluate a CRISPR/Cas9-Based Exon Excision Approach as a Future Treatment Option for -Associated Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is an inherited retinal disease (IRD) with an overall prevalence of 1 in 4000 individuals. Mutations in () are among the most frequent causes of non-syndromic autosomal recessively inherited RP and act via a loss-of-function mechanism. In light of the recent successes for other IRDs, we investigated the therapeutic potential of exon skipping for -associated RP.

Genetics, pathogenesis and therapeutic developments for Usher syndrome type 2.

Usher syndrome (USH) is a rare, autosomal recessively inherited disorder resulting in a combination of sensorineural hearing loss and a progressive loss of vision resulting from retinitis pigmentosa (RP), occasionally accompanied by an altered vestibular function. More and more evidence is building up indicating that also sleep deprivation, olfactory dysfunction, deficits in tactile perception and reduced sperm motility are part of the disease etiology. USH can be clinically classified into three different types, of which Usher syndrome type 2 (USH2) is the most prevalent.