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mRNA lipid nanoparticles for myocardial infarction

Award Number: R01HL183505
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/10/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2030

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mRNA lipid nanoparticles for myocardial infarction - PROJECT SUMMARY Myocardial infarction (MI) is the leading cause of death worldwide, occurring when a blockage in a coronary artery deprives heart tissue of oxygen, leading to cardiomyocyte death and increasing the risk of heart failure (HF). While current treatments focus on restoring blood flow, they often fail to promote effective vascularization and prevent adverse remodeling in the infarcted myocardium. Restoration of blood flow and tissue repair after MI critically depends on the formation of new, functional blood vessels. Vascular endothelial growth factor-A (VEGF-A) is a key driver of angiogenesis, essential for re- establishing perfusion in the ischemic myocardium. However, uncontrolled VEGF-A expression can result in abnormal, leaky vessels that exacerbate tissue damage. In parallel, the platelet-derived growth factor receptor beta (PDGFRβ) pathway contributes to vessel stabilization and fibrotic remodeling; its inhibition can reduce fibrosis and promote the development of a functional vascular network. However, there are currently no drugs to specifically inhibit PDGFRβ in the heart, making targeted siRNA delivery a potentially promising strategy. The ischemic environment further complicates repair by activating platelets and endothelial cells, which locally release thrombin—a central enzyme in the coagulation cascade that not only facilitates clot formation but also activates endothelial cells, fueling inflammation and impaired blood flow. To address these challenges, we propose developing conformation-sensitive platelet-hitchhiking lipid nanoparticles (CSPH-LNPs) to enable targeted co-delivery of VEGF-A mRNA and PDGFRβ siRNA to the infarcted myocardium. Our first objective is to screen and optimize a lipid nanoparticle formulation that effectively targets cardiac endothelial cells while minimizing off-target effects, including platelet activation. The second objective is to engineer a responsive CD61-targeting modification that enables CSPH-LNPs to hitchhike on platelets and release their therapeutic cargo precisely at the site of injury in response to local thrombin release. The final objective is to evaluate the therapeutic efficacy of CSPH-LNPs in promoting vascularization and functional recovery in a mouse model of MI. If successful, this project will introduce a novel, targeted therapy that not only enhances vascularization but also prevents pathological remodeling, offering a promising strategy to improve outcomes for MI patients and reduce the risk of heart failure.


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 = $632,081 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	1	8/11/2026	NEW	$632,081
														Subtotal = $632,081

Grand Total All Awards = $632,081

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mRNA lipid nanoparticles for myocardial infarction

Award Number: R01HL183505

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/10/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2030

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