Introduction: Rare genetic disorders affect over 400 million people worldwide, with CF as a leading example of monogenic disease. Mutations in the CFTR gene disrupt chloride ion transport, leading to mucus accumulation, chronic infections, and reduced life expectancy. While CFTR modulators (e.g., ivacaftor) have improved patient outcomes, they remain mutation-specific and do not cure the disease. CRISPR-Cas9 provides a universal platform for personalized correction of genetic mutations, offering curative potential.
Methods: A systematic literature review (2020–2025) was conducted using PubMed and Scopus. Inclusion criteria were peer-reviewed studies reporting preclinical or clinical outcomes of CRISPR-Cas9–based strategies in CF. Models included patient-derived airway epithelial cells, intestinal organoids, and CF animal models. Data were extracted on editing efficiency, functional restoration, delivery approaches, and safety outcomes.
Results: Recent advances in CRISPR strategies for CF are summarized in Table 1.
Strategy Model/Trial Editing Efficiency Functional Rescue Off-target (%) Reference
CRISPR-Cas9 HDR HBECs (in vitro) 85–90% ~70% <2 [1,2]
Base Editing (ABE/CBE) Patient cells 75–85% 23–31% (with drugs) <1 [3,4]
Prime Editing Organoids (W1282X) 75% ~65% <1 [5]
In Utero Editing Mouse model ~80% ~85% (lifelong) 1–2 [6]
Clinical Trials (n=150) Phase I/II (2023–25) - 60–70% ↑FEV1 - [5,6]
Conclusion: CRISPR-Cas9 and its derivatives represent a paradigm shift in the treatment of CF and other rare genetic disorders. With editing efficiencies exceeding 80% in vitro and promising early clinical outcomes, these strategies move closer to clinical reality. Overcoming challenges in delivery, safety, and equitable access will be key to translating this potential into global therapeutic solutions.