TY - JOUR T1 - Theratyping cystic fibrosis in vitro in ALI-culture and organoid models generated from patient-derived nasal epithelial Conditionally Reprogrammed Stem Cells JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00908-2021 SP - 2100908 AU - Sette, Giovanni AU - Lo Cicero, Stefania AU - Blaconà, Giovanna AU - Pierandrei, Silvia AU - Bruno, Sabina Maria AU - Salvati, Valentina AU - Castelli, Germana AU - Falchi, Mario AU - Fabrizzi, Benedetta AU - Cimino, Giuseppe AU - De Maria, Ruggero AU - Biffoni, Mauro AU - Eramo, Adriana AU - Lucarelli, Marco Y1 - 2021/01/01 UR - //www.qdcxjkg.com/content/early/2021/07/29/13993003.00908-2021.Abstract N2-问题囊性纤维化（CF）是由于囊性纤维化跨膜电导调节剂（CFTR）基因的致病变异所致。最近的改进实现了旨在恢复突变CFTR表达和功能的药理疗法。CFTR“调节器”彻底改变了CF治疗景观，尤其是最后批准的Trikafta。这种药物组合由FDA表示，最近由EMA指示，用于携带至少一份具有F508DEL致病变体的CFTR副本的基因型。然而，几种基因型尚未获得Trikafta治疗的资格。材料/患者和方法我们利用了一种创新的细胞方法，可以通过条件重编程（CRC）（CRC）从鼻内上皮干细胞（AESC）进行高效的体外扩张（AESC）。CF患者。这种方法与AESC衍生的个性化疾病模型的开发相结合，作为类器官和空气液体界面（ALI）培养物，非常适合CFTR药理测试。回报和回答我们完全验证了实验模型并实施了CFTR功能测定和生化CFTR蛋白表征，可以评估临床可用调节剂在恢复每个患者衍生的“ avatar”（THERateTyping）的CFTR成熟和功能方面的功效。用作对照的F508DEL纯合基因型证实了Trikafta的较高临床活性与较旧的调节剂相比。Trikafta在三种以前不符合调节剂处理的罕见基因型上表现出了功效，这为临床翻译开辟了道路。 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. ER -