Gene Therapy for Cystic Fibrosis: Progress and Challenges of Genome Editing

Abstract

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 (CFTR) gene, and their applications for the development of experimental models valuable for the advancement of CF therapies.

Anticipating New Treatments for Cystic Fibrosis: A Global Survey of Researchers

“…Then, we generated a list of their Digital Object Identifiers (DOIs) and imported it into the reference management software Citavi 6.1, where these references were downloaded in a PDF format and fully read. After this process, we considered 47 [ 6 , 8 , 9 , 10 , 20 , 22 , 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ] references appropriate to the study and used them in the literature review that allowed us to draft the survey questionnaire.…”

Remodelling of a bacterial immune system as the simple gene editing tool, Crispr-Cas, for food security and human health

“…Genetic lung diseases: Cystic Fibrosis (CF) is a genetic disease caused by a mutation that occurs in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The defective CFTR protein leads to an imbalance of water and ion flow in and out of cells, resulting in thick mucus that obstructs airways and traps bacteria (Maule et al, 2020). Researchers utilized CRISPR/Cas9 to inactivate the expression of the mutant human SP gene in an embryonic mouse model.…”

On the Corner of Models and Cure: Gene Editing in Cystic Fibrosis

“…Therefore, its use in many adult cell types is limited. For a schematic overview of the two repair pathways and their possible applications, we refer to ( Pranke et al, 2019 ; Maule et al, 2020 ).…”