International journal of molecular sciencesOct 16, 2026

Comparing Prime Editing and CRISPR Methods to Fix the CFTR-F508del Mutation in Patient-Derived Airway Stem Cells

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 17, 2026

Abstract

Correction of the F508del mutation in the CFTR gene was achieved with efficiencies up to 18.9% using gene editing techniques.

Both CRISPR-Cas9-mediated homology-directed repair and prime editing can correct the most common CF mutation.
The CRISPR-Cas9 method resulted in insertions and deletions in about 15% of edited alleles.
Prime editing caused minimal unintended modifications compared to CRISPR-Cas9.
Functional analysis indicated that prime editing restored CFTR channel conductance to levels comparable to existing triple therapies.
The low frequency of unwanted changes in prime editing suggests it may be a better candidate for gene therapy for cystic fibrosis.

Simplified

Gene editing therapy represents a promising strategy to permanently cure cystic fibrosis (CF). This paper presents the results of correcting the most common CF mutation, F508del, in the CFTR gene in airway basal cells (BCs) obtained from patients, using both classical CRISPR-Cas9-mediated homology-directed repair (HDR) and prime editing techniques. Our findings demonstrate that both methods achieve mutation correction with efficiencies reaching up to 18.9% of alleles in successfully transfected cells. However, the CRISPR-Cas9 approach results in insertions and deletions (indels) in approximately 15% of alleles at the editing site, whereas prime editing induced only minimal indel events. Functional analysis evaluating the effectiveness of gene editing revealed that prime editing of the F508del mutation in the CFTR gene-using the pegRNA4 combined with the PE2-NG variant-restores CFTR channel conductance, comparable to triple therapy with CFTR modulators (ivacaftor/tezacaftor/elexacaftor). While both prime editing and CRISPR-HDR resulted in successful correction of the CFTR-F508del mutation in patient BCs, prime editing exhibited a low frequency of unintended modifications both within and outside the editing locus, making this approach a promising candidate for the development of gene therapy strategies for CF.

Full Text

Full text is available at the source.

View Full Text ↗

Featured in

CRISPR Gene EditingIssue #59

Prime editing fixed a cystic fibrosis mutation with almost zero collateral damage

↗

Comparing Prime Editing and CRISPR Methods to Fix the CFTR-F508del Mutation in Patient-Derived Airway Stem Cells

Abstract

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the crispr gene editing brief