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Lung-targeting immunomodulatory mRNA-lipid nanoparticle system

Award Number: R21HL184087
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Lung-targeting immunomodulatory mRNA-lipid nanoparticle system - PROJECT SUMMARY Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury (ALI), characterized by uncontrolled inflammation, excessive pro-inflammatory cytokine expression, neutrophil infiltration, and damage to the alveolar-capillary barrier. Among the causes of ARDS, sepsis is the most prevalent, accounting for 32% of cases. Current management primarily relies on protective mechanical ventilation and supportive critical care. Despite advances, ARDS remains a leading cause of mortality, underscoring the urgent need for effective therapeutic interventions. Corticosteroids are widely used but are often accompanied by significant adverse effects. Alternative approaches have been explored, with IL-10 standing out as a potent pleiotropic cytokine that plays a critical role in modulating inflammation and maintaining immune homeostasis. IL -10 effectively suppresses LPS- and bacteria-induced pro-inflammatory cytokines. It showed promising results in ALI/ARDS treatment. However, its clinical translation has been hindered by suboptimal pharmacokinetics, instability, and non-specific distribution. To address these challenges, we propose developing a lung-targeted IL-10 mRNA therapy using our novel lung-targeting sulfonium lipid nanoparticle (sLNP) technology. Our hypothesis is that delivering IL-10 mRNA specifically to the lungs and inducing its expression at the injury site will enhance therapeutic efficacy while minimizing the risk of systemic side effects. Our pilot studies have demonstrated the efficacy and safety of IL-10 mRNA/sLNP in treating ALI/ARDS in mouse models. In this project, we aim to evaluate the safety, tissue distribution, and therapeutic potential of IL-10 mRNA/sLNP in a more clinically relevant swine model of sepsis-induced ARDS. The success of this study could transform ALI/ARDS management and pave the way for future innovations in targeted mRNA therapeutics for respiratory care.


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 = $448,250 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Lung Diseases Research	000	1	5/15/2026	NEW	$448,250
														Subtotal = $448,250

Grand Total All Awards = $448,250

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Lung-targeting immunomodulatory mRNA-lipid nanoparticle system

Award Number: R21HL184087

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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