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

The pre-messenger RNA (pre-mRNA) of Usher syndrome 2A (USH2A) exon 13 is a critical therapeutic target for treating vision loss associated with Usher syndrome type 2A and non-syndromic retinitis pigmentosa. The USH2A gene encodes usherin, a large basement membrane protein essential for the structural integrity and function of retinal photoreceptors and inner ear hair cells (UniProt: O75445). Mutations within exon 13, most notably the c.2299delG frameshift mutation, lead to the production of truncated, non-functional usherin, resulting in progressive retinal degeneration (PubMed: 33513341). Therapeutic intervention utilizes antisense oligonucleotides (ASOs), such as ulrevigersen (QR-421a), which bind specifically to the pre-mRNA to modulate splicing. This binding induces exon skipping, where exon 13 is excluded from the mature mRNA transcript. Since exon 13 is in-frame, its removal allows the cellular machinery to produce a slightly shortened but functional usherin protein, thereby preserving photoreceptor function and slowing disease progression (ProQR Therapeutics; ClinicalTrials.gov: NCT03780257). This approach represents a precision medicine strategy targeting the underlying genetic cause of the disorder at the RNA level.

Other names

USH2A pre-mRNAUsherin pre-mRNAUsher syndrome type IIa protein pre-mRNAUSH2A exon 13

Antisense oligonucleotide-mediated exon skipping