Gene Editing Shows Promise for Correction of CFTR Variants Currently Without Treatment
Research By: Patrick Harrison, PhD
Post Date: November 17, 2023 | Publish Date: Nov. 17, 2023
Pulmonary Medicine | Top Scientific Achievement
Cystic fibrosis (CF) is a genetic disorder marked by accumulation of thick mucus in various organs, particularly the lungs. CF can be caused by a wide variety of cystic fibrosis transmembrane conductance regulator (CFTR) gene variants. A triple combination of CFTR modulator drugs can improve lung function in many cases, but these drugs do not cure CF and are not effective for every CFTR variant.
A research study led by corresponding author Patrick Harrison, PhD, demonstrated two in vitro gene editing techniques targeted at W1282X, a CFTR variant for which no effective treatments currently exist. Adenine base editing was tested to directly correct the W1282X variant, and homology-independent targeted integration was tested to enable expression of CFTR mRNA without correcting W1282X.
Both gene editing approaches successfully restored CFTR protein expression and modestly increased CFTR channel activity, demonstrating exciting therCFTR apeutic potential for each technique. Adenine base editing of W1282X was commonly observed to cause another CFTR variant called R1283G via a process called bystander editing. However, a triple combination of modulators was found to restore CFTR channel activity that had been affected by the R1283G variant, suggesting the possibility of combining gene editing and triple combination therapy for clinical treatment of CF.
Future work will aim to develop therapeutics based on these promising gene editing approaches. Refinements that facilitate targeted delivery of these gene editors to the lungs of people with CF will be of particular interest.
Researchers from University College Cork (Ireland), Johns Hopkins University in Baltimore, MD, University of Lisboa (Portugal), and Lenox Hill Hospital in New York, NY contributed to this study.
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| Original title: | Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X |
| Published in: | Human Molecular Genetics |
| Publish date: | Nov. 17, 2023 |
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The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment.
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