# Tolerance-Inducing mRNA Nanoparticles to Treat Type 1 Diabetes

> **NIH NIH R56** · JOHNS HOPKINS UNIVERSITY · 2024 · $196,500

## Abstract

PROJECT SUMMARY
Type 1 diabetes (T1D) is a life-threatening autoimmune disease affecting over 1 million patients
in the United States that occurs when the immune system attacks and destroys insulin-
producing beta islet cells in the pancreas. Treatment of T1D requires a lifetime of constant
maintenance to avoid life-threatening complications. There is an urgent need for a therapy that
can engineer the immune system to prevent disease progression at early stages, prevent
damage to islet cells, and have a long-lasting and transformative effect on patients. One
method of achieving T1D-specific tolerance is to genetically engineer antigen-presenting cells
(APCs) to present disease-relevant antigen(s). Antigen presentation in the presence of
tolerogenic signals can lead to the maturation of disease-specific protective regulatory T cells
(Tregs). In particular, liver-resident APCs express low levels of activating co-stimulatory
molecules, and surrounding cells secrete immunosuppressive signals, making the liver a
tolerogenic environment. We hypothesize that non-viral transfection of APCs in the liver with
genes encoding T1D-specific autoantigens will promote safe and specific protective tolerance as
a tolerogenic vaccine for the prevention and treatment of autoimmune T1D. We will develop
biodegradable nanoparticles to safely and effectively program immune cells in vivo, including
APCs. We will first create and well-characterize the new nanobiotechnology and validate it in in
vitro models (Aim 1). We will then evaluate the nanobiotechnology in vivo in mouse models of
T1D (Aim 2). Finally, we will evaluate these NPs with human immune cells in vitro and in vivo,
bringing this technology closer to translation (Aim 3). This nanoparticle-based biotechnology is
designed to enable a safe and effective method of immune cell engineering to treat T1D.

## Key facts

- **NIH application ID:** 10908728
- **Project number:** 5R56DK137420-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Joshua Charles Doloff
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $196,500
- **Award type:** 5
- **Project period:** 2023-08-16 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908728

## Citation

> US National Institutes of Health, RePORTER application 10908728, Tolerance-Inducing mRNA Nanoparticles to Treat Type 1 Diabetes (5R56DK137420-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10908728. Licensed CC0.

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