Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research
Abstract
Since the development of the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator in 2012, these therapies have revolutionized patients' health. They are now the most effective treatment for people with cystic fibrosis (pwCF). In fact, elexacaftor/tezacaftor/ivacaftor and vanzacaftor/tezacaftor/deutivacaftor, the latest combination therapies consisting of a CFTR potentiator and two CFTR correctors, improved lung function by 14% in pwCF. Other modulator therapies targeting CFTR mRNA and/or protein are currently under preclinical/clinical investigation. However, due to the variant-specific nature of these therapies, about 10% of pwCF in Europe remains without effective treatment, and many treated pwCF experience various adverse events such as headaches, infections, hepatotoxicity, hypertension, and depression. Therefore, mutation-agnostic strategies such as gene therapy are needed. They could expand treatment eligibility for all pwCF and improve outcomes. In fact, nucleic acid delivery (e.g., pDNA, mRNA, oligonucleotides, genome editing) or targeting non-CFTR channels to restore ion transport represent promising future additional directions for CF therapy. This review aims to discuss a potential combination between gene therapy approaches and existing modulators to improve treatment eligibility, safety, and efficacy.
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BibTeX
@article{buin2026combining,
title = {{Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research}},
author = {Xavier Buin and Rosy Ghanem and Ines Pankonien and Frédéric Becq and Margarida Amaral and Tristan Montier},
journal = {Pharmaceutics},
year = {2026},
month = aug,
doi = {10.3390/pharmaceutics18081040},
url = {https://hal.science/hal-05797884v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research
AU - Xavier Buin
AU - Rosy Ghanem
AU - Ines Pankonien
AU - Frédéric Becq
AU - Margarida Amaral
AU - Tristan Montier
PY - 2026
DA - 2026/08/21
JO - Pharmaceutics
DO - 10.3390/pharmaceutics18081040
UR - https://hal.science/hal-05797884v1
AB - Since the development of the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator in 2012, these therapies have revolutionized patients' health. They are now the most effective treatment for people with cystic fibrosis (pwCF). In fact, elexacaftor/tezacaftor/ivacaftor and vanzacaftor/tezacaftor/deutivacaftor, the latest combination therapies consisting of a CFTR potentiator and two CFTR correctors, improved lung function by 14% in pwCF. Other modulator therapies targeting CFTR mRNA and/or protein are currently under preclinical/clinical investigation. However, due to the variant-specific nature of these therapies, about 10% of pwCF in Europe remains without effective treatment, and many treated pwCF experience various adverse events such as headaches, infections, hepatotoxicity, hypertension, and depression. Therefore, mutation-agnostic strategies such as gene therapy are needed. They could expand treatment eligibility for all pwCF and improve outcomes. In fact, nucleic acid delivery (e.g., pDNA, mRNA, oligonucleotides, genome editing) or targeting non-CFTR channels to restore ion transport represent promising future additional directions for CF therapy. This review aims to discuss a potential combination between gene therapy approaches and existing modulators to improve treatment eligibility, safety, and efficacy.
SN - 1999-4923
ER -