Ensinck Marjolein, Mottais Angélique, Detry Claire, Leal Teresinha, Carlon Marianne S
Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Institut de Recherche Expérimentale et Clinique, Louvain Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Brussels, Belgium.
Front Pharmacol. 2021 Apr 27;12:662110. doi: 10.3389/fphar.2021.662110. eCollection 2021.
Cystic fibrosis (CF) is a severe genetic disease for which curative treatment is still lacking. Next generation biotechnologies and more efficient cell-based and disease models are accelerating the development of novel therapies for CF. Gene editing tools, like CRISPR-based systems, can be used to make targeted modifications in the genome, allowing to correct mutations directly in the Cystic Fibrosis Transmembrane conductance Regulator () gene. Alternatively, with these tools more relevant disease models can be generated, which in turn will be invaluable to evaluate novel gene editing-based therapies for CF. This critical review offers a comprehensive description of currently available tools for genome editing, and the cell and animal models which are available to evaluate them. Next, we will give an extensive overview of proof-of-concept applications of gene editing in the field of CF. Finally, we will touch upon the challenges that need to be addressed before these proof-of-concept studies can be translated towards a therapy for people with CF.
囊性纤维化（CF）是一种严重的遗传疾病，目前仍缺乏治愈性治疗方法。新一代生物技术以及更高效的基于细胞和疾病的模型正在加速CF新型疗法的开发。基因编辑工具，如基于CRISPR的系统，可用于对基因组进行靶向修饰，从而直接纠正囊性纤维化跨膜传导调节因子（CFTR）基因中的突变。此外，利用这些工具可以生成更具相关性的疾病模型，这反过来对于评估基于基因编辑的CF新型疗法将具有极高价值。这篇批判性综述全面描述了目前可用的基因组编辑工具，以及用于评估这些工具的细胞和动物模型。接下来，我们将广泛概述基因编辑在CF领域的概念验证应用。最后，我们将探讨在这些概念验证研究转化为CF患者的治疗方法之前需要解决的挑战。
