Monday, June 30, 2025 6/30/2025

Optimizing Surgical Transplant of CFTR Gene-Corrected Human Basal Stem Cells to the Upper Airway

Award Number: R01HL151677
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Optimizing Surgical Transplant of CFTR Gene-Corrected Human Basal Stem Cells to the Upper Airway - PROJECT SUMMARY/ABSTRACT Cystic fibrosis (CF) is an autosomal recessive single-gene disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation, termed ∆F508, occurs in ~85% of CF patients. Because the CFTR gene encodes for an anion transport protein, CFTR mutations alter electrolyte and water transport, resulting in dense, pathologic, mucous and other secretions. The most harmful effects of CFTR dysfunction occur in the respiratory system, with recurrent infections and inflammation of the upper and lower airways. Despite substantial progress with medical therapies, there remains a tremendous unmet need for improved, durable therapies for CF. For the past 3 years, our collaborative group of complementary scientists and physicians has determined to develop a novel, stem cell-based treatment strategy for patients suffering from CF. For several critical reasons, we directed our efforts to cell-based therapy of CF upper airway disease using ex vivo-expanded, primary human airway basal stem cells, termed ABCs. The first major milestone was to utilize CRISPR/Cas9 genome editing technology to efficiently correct the ∆F508 mutation in ABCs cultured from CF patients undergoing sinus surgery. This gene correction approach has led to significant restoration of chloride anion transport from 0-3% to 30-40% in ABCs. This encouraging, and newly published, development now provides a pre-clinical roadmap for re-introducing CFTR gene-corrected ABCs into in vivo contexts as a stem cell replacement therapy. In this proposal, we will rigorously determine the most efficient, biomaterial platform for ex vivo-to-in vivo transplant and engraftment of human ABCs, and assess the behavior of gene-corrected ABCs in the lab and live animal model using a microsurgical model system of upper airway transplantation that we have developed. The experiments outlined are essential pre-clinical steps in order to translate this approach to CF patients to generate an innovative and possibly transformative therapy for patients with CF, and the first stem cell-based therapy for human airway disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $418,256 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	000	5	1/16/2025	NON-COMPETING CONTINUATION	$418,256
														Subtotal = $418,256

Issue Date FY: 2024 ( Subtotal = $458,061 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	000	4	1/11/2024	NON-COMPETING CONTINUATION	$420,667
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	001	4	6/14/2024	NON-COMPETING CONTINUATION	$37,394
														Subtotal = $458,061

Issue Date FY: 2023 ( Subtotal = $469,923 )
2023	2023	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	000	3	1/10/2023	NON-COMPETING CONTINUATION	$422,931
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	001	3	3/10/2023	NON-COMPETING CONTINUATION	$46,992
														Subtotal = $469,923

Issue Date FY: 2022 ( Subtotal = $470,100 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	000	2	1/10/2022	NON-COMPETING CONTINUATION	$423,089
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	003	2	6/15/2022	NON-COMPETING CONTINUATION	$47,011
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	002	2	3/15/2022	NON-COMPETING CONTINUATION	$0
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	001	1	3/8/2022	NEW	$0
														Subtotal = $470,100

Issue Date FY: 2021 ( Subtotal = $529,683 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Lung Diseases Research	000	1	3/1/2021	NEW	$529,683
														Subtotal = $529,683

Grand Total All Awards = $2,346,023

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Optimizing Surgical Transplant of CFTR Gene-Corrected Human Basal Stem Cells to the Upper Airway

Award Number: R01HL151677

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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