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

The F508del-mutated CFTR mRNA is the messenger RNA transcript derived from the cystic fibrosis transmembrane conductance regulator (CFTR) gene harboring a specific three-base pair deletion (CTT). This mutation results in the loss of a phenylalanine residue at position 508 of the CFTR protein, which is the primary cause of cystic fibrosis in the majority of patients (NIH, 2023). The presence of this mutation in the mRNA leads to the production of a misfolded protein that is recognized by the endoplasmic reticulum-associated degradation (ERAD) pathway and destroyed before reaching the cell surface (UniProt, 2024). While small-molecule correctors target the protein product, the mRNA itself is a target for novel genetic therapies such as antisense oligonucleotides (ASOs) like eluforsen, which aim to restore the reading frame or repair the sequence through RNA-level editing (PubMed, 2020). Additionally, mRNA-based therapeutic strategies involve delivering functional, non-mutated CFTR mRNA to lung epithelial cells to bypass the endogenous mutated transcript entirely (Cystic Fibrosis Foundation, 2024). Targeting the mRNA offers a potential way to restore chloride channel function and improve mucociliary clearance, addressing the underlying cause of the progressive lung disease and multi-organ dysfunction characteristic of cystic fibrosis. Successful therapeutic intervention requires overcoming challenges related to the delivery of nucleic acids to the thick, dehydrated mucus layer typical of the cystic fibrosis lung.

Other names

CFTR deltaF508 mRNAF508del-CFTR transcriptCFTR (c.1521_1523delCTT) mRNA

Antisense oligonucleotide-mediated RNA repair, mRNA replacement therapy, and restoration of functional CFTR protein expression.