Cystic fibrosis transmembrane conductance regulator (CFTR) exon 23 3' splice site (CFTR exon 23 3'ss)

The CFTR exon 23 3' splice site is a regulatory sequence in the pre-mRNA of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located at the junction of intron 22 and exon 23 (Kim et al., 2022). It is a therapeutic target for splice-switching antisense oligonucleotides (ASOs) designed to treat cystic fibrosis (CF) caused by the W1282X nonsense mutation (Michaels et al., 2022). By binding to this site, ASOs sterically hinder the splicing machinery, inducing the skipping of exon 23 during mRNA processing (Kim et al., 2022). Because exon 23 is a symmetrical, in-frame exon, its removal eliminates the premature termination codon (PTC) without causing a frameshift, thereby bypassing nonsense-mediated mRNA decay (NMD) (Oren et al., 2022). This results in the production of a truncated but partially functional CFTR protein isoform, CFTR-Δex23, which can be further activated by CFTR modulators like Trikafta (Kim et al., 2022; Michaels et al., 2022). This approach represents a precision medicine strategy for CF patients with nonsense mutations who do not respond to standard therapies (Frontiers in Pharmacology, 2023).

Other names

CFTR exon 23 acceptor siteCFTR intron 22-exon 23 junctionCFTR 3' splice site of exon 23

Induction of exon skipping via steric hindrance of the splicing machinery at the 3' splice site to bypass nonsense mutations and prevent nonsense-mediated decay (Kim et al., 2022).