Genome Editing for Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is a monogenic recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator gene (CFTR). Remarkable progress in basic research has led to the discovery of highly effective CFTR modulators. Now ~90% of CF patients are treatable. However, these modulator therapies are not curative and do not cover the full spectrum of CFTR mutations. Thus, there is a continued need to develop a complete and durable therapy that can treat all CF patients once and for all. As CF is a genetic disease, the ultimate therapy would be in-situ repair of the genetic lesions in the genome. Within the past few years, new technologies, such as CRISPR/Cas gene editing, have emerged as an appealing platform to revise the genome, ushering in a new era of genetic therapy. This review provided an update on this rapidly evolving field and the status of adapting the technology for CF therapy.

Keywords: CFTR; CRISPR/Cas; cystic fibrosis; gene editing; genome editing.

Figure 1

Gene editor delivery from an epithelial lumen. Potential barriers to overcome to achieve highly efficient gene editor delivery from an epithelial lumen.

Figure 2

Gene editor delivery via circulation. Potential barriers to overcome to achieve highly efficient gene editor delivery from the circulation.