Cystic fibrosis transmembrane conductance regulator exon 23 splice sites (CFTR exon 23 splice sites)

The target refers to the splice-site sequences flanking exon 23 (legacy numbering, currently exon 26) of the CFTR pre-mRNA. This region is a therapeutic target for splice-switching antisense oligonucleotides (ASOs) designed to treat Cystic Fibrosis (CF) caused by nonsense mutations, particularly the W1282X mutation [1, 3]. The W1282X mutation introduces a premature stop codon that triggers nonsense-mediated decay (NMD), resulting in low mRNA levels and a non-functional protein. Because exon 23 is a symmetrical, in-frame exon, its removal via ASO-induced skipping preserves the reading frame [1, 4]. The resulting mRNA isoform, CFTR-Δex23, is NMD-resistant and produces a protein that retains partial chloride channel activity, which can be further enhanced by CFTR modulators [2, 3]. This strategy represents a precision medicine approach for CF patients who do not benefit from standard modulator therapies [1, 5].

Other names

CFTR exon 23 pre-mRNACFTR exon 26 splice sitesW1282X target regionCFTR exon 23 splice junctions

Splice-switching to induce exon skipping and evade nonsense-mediated decay (NMD)