%0期刊文章%A Sette, Giovanni %A Lo Cicero, Stefania %A Blaconà， Giovanna %A Pierandrei, Silvia %A Bruno, Sabina Maria %A Salvati, Valentina %A Castelli, Germana %A Falchi, Mario %A Fabrizzi, Benedetta %A西米诺，Giuseppe %A De Maria, Ruggero %A Biffoni, Mauro %A Eramo, Adriana %A Lucarelli, Marco %T异型性囊性纤维化在体外问题:囊性纤维化(CF)是由囊性纤维化跨膜传导调节基因(CFTR)的致病变异引起的。最近的改进使药理学治疗能够恢复突变的CFTR表达和功能。CFTR“调节剂”已经彻底改变了CF治疗领域，特别是最近批准的Trikafta。该药物组合被FDA和最近的EMA指定为携带至少一个CFTR拷贝的F508del致病变体的基因型。然而，一些基因型还不适合Trikafta治疗。材料/患者和方法我们利用一种创新的细胞方法，通过条件重编程(CRC)从CF患者的鼻刷中高效地体外扩增气道上皮干细胞(AESC)。这种方法，加上aesc衍生的个性化疾病模型的开发，如类器官和气液界面(ALI)培养，显示非常适合CFTR药物测试。结果和问题的答案我们充分验证了实验模型，并实施了CFTR功能测定和CFTR蛋白生化表征，从而评估了临床可用的调节剂在恢复CFTR成熟和每个患者来源的“化身”(异型)功能方面的功效。F508del纯合基因型作为对照，证实Trikafta与旧的调节剂相比具有更高的临床活性。Trikafta还对三种以前不适合调节性治疗的罕见基因型显示了疗效，为临床转译开辟了道路。 Finally, encouraging results for innovative drug combinations were also obtained.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Giovanni Sette has nothing to disclose.Conflict of interest: Stefania Lo Cicero has nothing to disclose.Conflict of interest: Giovanna Blaconà has nothing to disclose.CConflict of interest: Silvia Pierandrei has nothing to disclose.Conflict of interest: Sabina Maria Bruno has nothing to disclose.Conflict of interest: Valentina Salvati has nothing to disclose.Conflict of interest: Germana Castelli has nothing to disclose.Conflict of interest: Mario Falchi has nothing to disclose.Conflict of interest: Benedetta Fabrizzi has nothing to disclose.Conflict of interest: Giuseppe Cimino has nothing to disclose.Conflict of interest: Ruggero De Maria has nothing to disclose.Conflict of interest: Mauro Biffoni has nothing to disclose.Conflict of interest: Adriana Eramo has nothing to disclose.Conflict of interest: Marco Lucarelli has nothing to disclose. %U //www.qdcxjkg.com/content/erj/early/2021/07/29/13993003.00908-2021.full.pdf