Tuesday, January 6, 2026 1/6/2026

Exogenic organs in gene edited pigs

Award Number: R01AI187293
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/20/2024
PERIOD OF PERFORMANCE END DATE: 10/31/2029

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Exogenic organs in gene edited pigs - PROJECT SUMMARY Endstage heart failure is a common cause of death in the U.S. and worldwide. The only curative therapy for end-stage heart disease is heart transplantation. Millions of patients (worldwide) could benefit from such therapy but are not eligible for transplantation due to limited donor organ availability. Therefore, there is an urgent need to develop alternative organ sources for cardiac transplantation. The long range goal and the clinical significance of this proposal are to use our newly engineered NKX2-5/TBX5/HAND2 knockout pigs as hosts ultimately for the production of personalized human hearts for clinical applications. The goal of the current application is to establish a nonhuman primate platform in a pig that would provide the feasibility for engineering a humanized heart in a gene edited pig. Our previous publications demonstrate the rationale and feasibility for our approach. Using CRISPR/Cas9 gene editing technology, we have established that NKX2- 5/TBX5/HAND2 mutant porcine embryos lack a heart and are lethal early during development. Using blastocyst complementation and SCNT we have further demonstrated that we can rescue the null phenotype and produce a viable chimeric pig with normal cardiac function. In these proposed studies, we will utilize a number of emerging technologies to engineer a paradigm shifting nonhuman primate heart in a genetically modified porcine surrogate. To examine our hypotheses, we will address the following specific aims: Specific Aim #1: To examine the capacity of GFP-labeled MHC mismatched porcine stem cells to rescue the porcine NKX2-5/TBX5/HAND2 null embryo; Specific Aim #2: To examine the capacity of interspecies (macaque iPSCs) stem cells to rescue the NKX2-5/TBX5/HAND2 null porcine host in vitro and Specific Aim #3: To generate a macaque heart in the NKX2-5/TBX5/HAND2 null porcine host. In these studies, we will use state-of-the-art gene technologies and macaque GFP-labeled stem cell populations to engineer a nonhuman primate heart in a gene edited pig. This nonhuman primate large animal model will be an important resource for regenerative medicine and will serve as a platform for generating personalized humanized porcine models. This strategy has the capacity to have a profound impact on the development of emerging therapies for endstage heart failure and transplantation. Given the tremendous morbidity and mortality of cardiovascular disease in our society, this proposal could have a transformative impact on the field of cardiac transplantation and the democratization of organ availability for our patients.


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: 2026 ( Subtotal = $769,995 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	2	11/26/2025	NON-COMPETING CONTINUATION	$769,995
														Subtotal = $769,995

Issue Date FY: 2025 ( Subtotal = $746,895 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	1	11/20/2024	NEW	$746,895
														Subtotal = $746,895

Grand Total All Awards = $1,516,890

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Exogenic organs in gene edited pigs

Award Number: R01AI187293

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 11/20/2024

PERIOD OF PERFORMANCE END DATE: 10/31/2029

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