Usher syndrome type 2A exon 13 pre-messenger RNA (USH2A exon 13 pre-mRNA)

Usher syndrome type 2A (USH2A) exon 13 pre-messenger RNA (pre-mRNA) is a molecular target for antisense oligonucleotide (ASO) therapy designed to treat inherited retinal degeneration. The USH2A gene encodes usherin, a protein critical for the structural integrity of photoreceptors in the retina and hair cells in the inner ear (UniProt O75445). Mutations in exon 13, such as the common c.2299delG frameshift mutation, result in the production of a truncated, non-functional protein, leading to the clinical manifestations of Usher syndrome type 2A and non-syndromic retinitis pigmentosa (PubMed: 32610315). By targeting the pre-mRNA transcript, therapeutic agents like ulrevigersen (QR-421a) modulate the splicing machinery to exclude the mutation-containing exon 13 from the final mRNA. This "exon skipping" approach allows for the translation of a slightly shorter but functional usherin protein, which aims to preserve vision in affected patients (PubMed: 34107144). Clinical evaluation of this target involves monitoring retinal structure and visual function to assess the efficacy of restoring usherin expression (ClinicalTrials.gov NCT03780257). The target is specifically localized to the nucleus where splicing occurs, making it accessible to ASOs delivered via intravitreal injection. Success in targeting this pre-mRNA represents a significant advancement in precision medicine for rare genetic sensory disorders.

Other names

USH2A pre-mRNAUsherin pre-mRNA exon 13USH2A exon 13

Antisense oligonucleotide-mediated exon skipping to restore the reading frame and produce a functional protein