Department of Cellular Computational Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy.
National Council of Research, CNR, 38123 Trento, Italy.
Int J Mol Sci. 2020 May 30;21(11):3903. doi: 10.3390/ijms21113903.
Since the early days of its conceptualization and application, human gene transfer held the promise of a permanent solution to genetic diseases including cystic fibrosis (CF). This field went through alternated periods of enthusiasm and distrust. The development of refined technologies allowing site specific modification with programmable nucleases highly revived the gene therapy field. CRISPR nucleases and derived technologies tremendously facilitate genome manipulation offering diversified strategies to reverse mutations. Here we discuss the advancement of gene therapy, from therapeutic nucleic acids to genome editing techniques, designed to reverse genetic defects in CF. We provide a roadmap through technologies and strategies tailored to correct different types of mutations in the cystic fibrosis transmembrane regulator ( gene, and their applications for the development of experimental models valuable for the advancement of CF therapies.
自其概念化和应用的早期以来，人类基因转移承诺为囊性纤维化 (CF) 等遗传疾病提供永久性解决方案。这个领域经历了热情和不信任的交替时期。允许使用可编程核酸内切酶进行特定部位修饰的精细技术的发展，使基因治疗领域得以高度复兴。CRISPR 核酸内切酶和衍生技术极大地促进了基因组操作，提供了多种策略来逆转突变。在这里，我们讨论了旨在纠正 CF 中遗传缺陷的基因治疗的进展，从治疗性核酸到基因组编辑技术。我们提供了一条通过技术和策略的路线图，这些技术和策略旨在纠正囊性纤维化跨膜调节剂 (CFTR 基因)中的不同类型突变，并将其应用于开发对 CF 治疗进展有价值的实验模型。
