Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA (F508del mutation) (CFTR mRNA (F508del))

The CFTR mRNA containing the F508del mutation is the messenger RNA transcript of the cystic fibrosis transmembrane conductance regulator gene harboring a three-nucleotide deletion (CTT) at position 1521-1523 (UniProt P13569). This mutation leads to the loss of a phenylalanine residue at position 508 of the CFTR protein, causing the protein to misfold and be degraded prematurely in the endoplasmic reticulum (PubMed: 28846095). As a therapeutic target, this specific mRNA sequence is addressed using RNA-based strategies such as antisense oligonucleotides (ASOs) or mRNA replacement therapies (PubMed: 31513778). These approaches aim to either repair the transcript or provide a functional wild-type version to restore chloride channel activity in the apical membrane of epithelial cells. Restoring CFTR function is critical for maintaining the hydration of airway surfaces and preventing the thick mucus buildup characteristic of cystic fibrosis. Current research focuses on improving the delivery of these RNA molecules to the lungs and ensuring long-term stability and expression (StatPearls: Cystic Fibrosis). Successful modulation of this target could provide a mutation-specific or universal treatment for patients who do not respond well to traditional small-molecule modulators.

Other names

CFTR F508del mRNACystic fibrosis transmembrane conductance regulator messenger RNA (F508del)deltaF508 CFTR mRNAc.1521_1523delCTT mRNACFTR deltaF508 mRNA

Antisense oligonucleotide-mediated RNA repair or mRNA replacement to restore functional CFTR protein expression.