# A Non-Viral Genetic Vaccine for Prevention and Treatment of Multiple Sclerosis

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $245,625

## Abstract

PROJECT SUMMARY
 Multiple sclerosis (MS) is the leading cause of non-traumatic disability in young adults in the United
States. In MS, the immune system attacks autoantigens in the myelin sheath of the central nervous system
(CNS), leading to neurological degeneration, and there is currently no cure. A treatment for MS that does not
cause general immunosuppression is urgently needed. One leading strategy for this is to induce antigen-specific
immune tolerance, which can prevent immune responses against the myelin sheath without having a systemic
suppressive effect. In order to accomplish this, we propose to use synthetic, biodegradable polymeric
nanoparticles to deliver mRNA encoding the MS autoantigen myelin oligodendrocyte glycoprotein
(MOG) to antigen-presenting cells (APCs) as a tolerogenic nanoparticle (NP)-based vaccine. By
engineering the NPs to selectively target the liver, where APCs express low levels of activating signals and
surrounding cells secrete high concentrations of immunosuppressive signals, we will enable presentation of the
MOG antigen to T cells in a tolerogenic context. As a second layer of safety to prevent inadvertent immune
stimulation targeting the MOG antigen, we will co-deliver an immunosuppressive agent. This is designed to lead
to expansion of MOG-specific regulatory T cells (Tregs), which will provide antigen-specific protective
immunosuppression. At the same time, in the absence of activating co-stimulatory molecules, the transfected
APCs can also cause anergy or death of MOG-specific Th1, Th17, and CD8+ T cells, thereby preventing such
cells from causing disease. This proposal will further optimize the NP formulations to maximize APC transfection,
minimize unintended immune activation, and further improve in vivo delivery of NPs selectively. This NP
technology represents an innovative vaccine platform for preventing or treating MS, with advantages of safety
and ease of manufacture compared to other related technologies, such as the use of viral vectors for gene
delivery.

## Key facts

- **NIH application ID:** 10374165
- **Project number:** 5R21AI160738-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jordan Green
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $245,625
- **Award type:** 5
- **Project period:** 2021-03-17 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374165

## Citation

> US National Institutes of Health, RePORTER application 10374165, A Non-Viral Genetic Vaccine for Prevention and Treatment of Multiple Sclerosis (5R21AI160738-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10374165. Licensed CC0.

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