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Polymer-derived biomaterials for mRNA delivery to induce antigen-specific immunetolerance

Award Number: R01EB037656
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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Polymer-derived biomaterials for mRNA delivery to induce antigen-specific immunetolerance - Project Summary The immune system protects people from pathogens. However, it sometimes generates abnormal immune reactions against harmless environmental antigens or patient’s own antigens, leading to allergies or autoimmune diseases, respectively. These hypersensitivity disorders affect millions of Americans and are life-threatening in severe conditions. Current therapeutic strategies often require lifelong treatment and/or broad immunosuppression, causing adverse effects. The induction of antigen-specific immune tolerance is a promising strategy to treat hypersensitivity without compromising immune protection because this strategy either specifically eliminates the disease-related immune cells or restrains their hypersensitive response, leaving the immune system intact. The tolerance may last lifelong once established. Although progress has been made in this area, technologies that induce efficient antigen-specific immune tolerance remain to be developed. The key to success in tolerance induction is the precise modulation of targeted immune cells. Compared to small drug molecules, a set of proteins translated from delivered messenger RNAs (mRNAs) in immune cells can work coordinately to transform the cells in a more precise manner. However, mRNA delivery for inducing immune tolerance has not been established. This is because most reported mRNA delivery nanocarriers cause inflammatory response and/or cannot target the right antigen-presenting cells (APCs) to initiate the process of tolerance induction. We have recently shown that our polymeric nanoparticle could efficiently target liver sinusoidal endothelial cells (LSECs), which are a type of APCs naturally helping the immune system maintain tolerance. We hypothesize that nanocarriers derived from this polymeric nanoparticle can co-deliver antigens and mRNAs encoding tolerogenic proteins to LSECs to induce antigen-specific immune tolerance. It is worth noting that our strategy is not mRNA vaccine because antigenic peptides will be delivered directly and are not translated from the delivered mRNA. In our preliminary studies, we demonstrated that such a nanocarrier can deliver mRNA to LSECs in mice for protein translation after systemic administration, and the nanocarrier loaded with an antigen can inhibit the antigen-specific T cells from being restimulated after in vivo treatment of mice. Furthermore, our delivery system exhibited highly promising efficacy in a mouse model of autoimmune disease in a preliminary study. We will test our hypothesis by 1) developing novel nanomaterials encapsulating antigen and mRNA and evaluating them in vitro; 2) investigating the biodistribution of selected nanocarriers and their tolerogenic potential in vivo; 3) evaluating nanomaterial engineering in regulating immune tolerance in disease models. Our proposed study is expected to have a broad scientific and societal impact by achieving antigen- specific immune tolerance.


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 = $547,836 )
2026	2026	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	8/13/2026	NEW	$547,836
														Subtotal = $547,836

Grand Total All Awards = $547,836

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Polymer-derived biomaterials for mRNA delivery to induce antigen-specific immunetolerance

Award Number: R01EB037656

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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