Genetic therapies in cystic fibrosis

Curr Opin Pulm Med. 2023 Nov 1;29(6):615-620. doi: 10.1097/MCP.0000000000001019. Epub 2023 Sep 12.


Purpose of review: Advances in cystic fibrosis (CF) therapies over the past decade pivotally changed the morbidity and mortality of CF with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators that rescue dysfunctional CFTR protein in individuals with eligible genotypes. However, a significant proportion of the CF population is in need of alternative treatment strategies to address CFTR variants that are ineligible for therapeutic protein correction and/or potentiation. Current drug development efforts of nucleic-acid based therapies (i.e., DNA and RNA based therapies) in CF are informed by historic challenges of CF gene therapy trials, recent FDA guidance informed by non-CF gene therapy trials, and advances in therapeutic applications related to severe acute respiratory syndrome coronavirus 2 vaccine development. These historic and timely developments are of significant relevance for advancing genetic therapies in CF.

Recent findings: This article reviews the main themes of semi-permanent genetic therapy strategies covering recent literature focused on: adenovirus and adeno-associated virus vector delivery, advances in lentivirus vector use and safety considerations, mRNA delivery and antisense oligonucleotide drug development.

Summary: Currently, drug development and clinical trials for genetic therapies in CF are rapidly progressing. This review aims to increase the foundational knowledge of CF genetic therapies.

Publication types

  • Review

MeSH terms

  • COVID-19* / therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Cystic Fibrosis* / genetics
  • Cystic Fibrosis* / metabolism
  • Cystic Fibrosis* / therapy
  • Genetic Therapy
  • Genotype
  • Humans
  • Mutation


  • Cystic Fibrosis Transmembrane Conductance Regulator