Research Resources

Robust, validated cell, disease and animal models are critical to accelerate research and drug discovery and development for CFTR nonsense mutations. A lack of model systems to support investigation of CFTR nonsense mutations has previously served as a barrier to progress. At Emily’s Entourage, we are deeply committed to investing in and developing the most rigorously tested model systems and research resources. 

CFTR nonsense mutation resources available to the research community include:

Complementary DNA Constructs

cDNA constructs expressing mutated (W1282X-CFTR) and truncated CFTR produced by the W1282X-CFTR mutation (CFTR₁₂₈₁) are available from Peter Haggie, PhD, University of California, San Francisco. Constructs were generated in pcDNA3.1/Zeo(+), and can be readily subcloned into alternative vectors. Further information is available here. Generation of these cDNA constructs was supported by Emily’s Entourage. 

Cell Models

Rat thyroid epithelial cell models

• Fischer rat thyroid (FRT) cell models expressing W1282X-CFTR and CFTR₁₂₈₁ (with the EYFP-H148Q/I152L/F46L halide-sensitive reporter) are available from Peter Haggie, PhD, University of California, San Francisco. These cell models are amenable to fluorescence and electrophysiological assessment of CFTR activity. Further information is available here. Generation of these cell models was supported by Emily’s Entourage.

Immortalized airway epithelial cell models  

• Immortalized CFBE41o- airway epithelial cells expressing W1282X-CFTR or CFTR₁₂₈₁ with engineered triplet HA epitope tags, to facilitate biochemistry and cell surface presentation, have been generated by Gergerly Lukacs, MD, PhD, McGill University. 

Gene edited airway epithelial cell models

• Gene edited immortalized 16HBE14o- human bronchial epithelial cells expressing W1282X-CFTR (and additional CFTR mutations) have been generated by the Cystic Fibrosis Foundation Therapeutics Lab and is available here. 

Growth enhanced airway epithelial cell models

• Near-native, growth-enhanced homozygous W1282X-CFTR nasal epithelial cells expressing a proto-oncogene (Bmi-1) and the catalytic subunit of telomerase (hTERT) are available from Scott Randell, PhD, University of North Carolina, Chapel Hill. Further information is available here. Generation of these cell models was supported by Emily’s Entourage. 

Human primary airway epithelial cells and intestinal organoids

• Primary nasal, lung, and intestinal cells with two nonsense mutations (including homozygous W1282X/W1282X cells) are available from CFF’s RARE cell collection at the Cystic Fibrosis Foundation Therapeutics (CFFT) Lab. Cells will be distributed based on availability and evaluation of a short (~half page) research plan that will be evaluated for scientific merit. For specific genotype availability, please contact Jessica Stach. MTA requests can be initiated via the CFFT Lab here.

Human primary nasal epithelial cells and stem cell models

• A biobank of nasal epithelial cells and induced pluripotent stem cells (iPSCs) isolated from individuals living with CF, including those homozygous or heterozygous for the W1282X and/or G542X mutations, is available from The CF Canada-SickKids Program in Individual Therapy (CFIT). Certain iPSCs have been CrispR-edited to generate isogenic controls. 

Rectal organoids

• Rectal organoids derived from homozygous W1282X-CFTR subjects are maintained by and available from Hubrecht Organoid Technology and the Cystic Fibrosis Foundation Therapeutics Lab.

Stem cell model

• Induced pluripotent stem cells homozygous for the W1282X-CFTR mutation are available from the Diamond Lab, University of Pennsylvania. 

Murine Models

Murine models to investigate Cystic Fibrosis (CF) pathology, including models of CF caused by nonsense mutations are available from Craig Hodges, PhD, at the Case Western Reserve University Cystic Fibrosis Mouse Model Core.

For questions about these resources, please Contact Us.