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

Marjolein Ensinck,Marianne S Carlon,Teresinha Leal,Claire Detry,Angélique Mottais

doi:10.3389/fphar.2021.662110

Abstract

Cystic fibrosis (CF) is a severe genetic disease for which curative treatment is still lacking. Next generation biotechnologies and more efficient cell-based and in vivo 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 (CFTR) 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.

Highlights

Cystic fibrosis (CF) is a rare genetic disease affecting approximately 80,000 people worldwide (Jackson and Goss, 2018)
It has transformed therapeutic development efforts to redirect their focus to the last 10% of patients carrying two minimal function mutations, not responsive to the market approved CFTR modulators developed by Vertex Pharmaceuticals
The most recent of these trials was based on the delivery of monthly doses of a liposome CFTR cDNA formulation, and led to a stabilization in lung function, providing hope that further improvements in gene therapy tools will increase the efficacy of such a therapy

Summary

Introduction

Cystic fibrosis (CF) is a rare genetic disease affecting approximately 80,000 people worldwide (Jackson and Goss, 2018). We will discuss the most recent advances in gene editing with respect to both the development of human-relevant disease models of CF as well as proof of concept studies that have shown the feasibility and safety of correcting a variety of CFTR mutations.

Results

Conclusion