In the clinically successful era of CFTR modulators and Theratyping, 10–20% of individuals with cystic fibrosis (CF) may develop disease due to CFTR mutations that remain undruggable. These individuals produce low levels of CFTR mRNA and/or not enough protein to be rescued with modulator drugs. Alternative therapeutic approaches to correct the CFTR defect at the mRNA level using nucleic acid technologies are currently feasible; e.g., oligonucleotides platforms, which are being rapidly developed to correct genetic disorders. Drug-like properties, great specificity, and predictable off-target effects by design make oligonucleotides a valuable approach with fewer clinical and ethical challenges than genomic editing strategies. Together with personalized and precision medicine approaches, oligonucleotides are ideal therapeutics to target CF-causing mutations that affect only a few individuals resilient to modulator therapies.

在 CFTR 调节剂和治疗分型的临床成功时代，10% 至 20% 的囊性纤维化 (CF) 患者可能会因 CFTR 突变而发生疾病，这些突变仍然无法治疗。这些个体产生低水平的 CFTR mRNA 和/或没有足够的蛋白质来用调节剂药物拯救。使用核酸技术在 mRNA 水平纠正 CFTR 缺陷的替代治疗方法目前是可行的；例如，寡核苷酸平台正在迅速开发以纠正遗传疾病。类药物特性、高特异性和可预测的脱靶效应使寡核苷酸成为一种有价值的方法，与基因组编辑策略相比，其临床和伦理挑战更少。结合个性化和精准医疗方法，