The discovery of pharmacologic cystic fibrosis transmembrane conductance regulator (CFTR) modulators has transformed the landscape for cystic fibrosis (CF) treatment worldwide. A substantial fraction of CF patients can benefit from the small molecule ivacaftor and its partner drugs. However, around 10 percent of patients are not eligible for such therapy, either because their CFTR genotype is refractory to existing drugs or because they cannot tolerate modulator therapy4. For these patients, there is an urgent need for alternative strategies to restore CFTR function.

Our goals for this project are to (1) develop delivery vehicles that can transduce base editors into primary HBE cells, (2) establish base editing in differentiated ALI model of airway epithelium, and (3) deliver base editors for in vivo correction of a CFTR mutation.

This project is part of the research program Advancing Delivery of Novel Genome Editing Enzymes to Correct Orphan CF Mutations (overall PI: Urnov). Also see Cell-specific assessment of delivery and editing by cystic-fibrosis-tailored base editors.

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Learn more about the IGI Delivery Collective, a collaborative effort working to develop new technology for delivery of CRISPR-based therapies.