# Engineered DNA-particles to model immune events in systemic lupus erythematosus

> **NIH NIH R21** · DUKE UNIVERSITY · 2024 · $197,170

## Abstract

Summary/Abstract
Systemic lupus erythematosus (SLE or lupus) is a prototypic autoimmune disease that causes severe systemic
manifestations, of which nephritis is the major cause of morbidity and mortality. SLE primarily affects young
women, with African American patients showing much earlier and more severe disease than European
Americans. An important feature of SLE is the expression of antibodies to nuclear molecules (anti-nuclear
antibodies (ANAs)). ANAs provide serological markers for diagnosis, classification, and disease activity. While
there has been extensive study of the pathogenesis of SLE, much remains unknown about the underlying
mechanisms that promote inflammation and renal injury. As a result, SLE treatment is empiric and frequently
ineffective. Current treatments can cause permanent organ damage and severe side effects, providing a strong
rationale for the mechanistic studies necessary for more effective and less toxic therapies. In patients as well as
animal models of SLE, the formation of immune complexes by ANAs is a key step in inflammation and injury. Of
ANAs that can form immune complexes, antibodies to DNA (anti-DNA) have a prominent and well-validated role
in nephritis, as shown by the isolation of anti-DNA from affected kidneys of patients, as well as the induction of
nephritis in animal models by administration of monoclonal anti-DNA antibodies. While most models for immune
complexes are based on antibody interaction with soluble protein or nucleic acid antigens of relatively low
molecular weight, recent research suggests that immune complexes in SLE form on cell-generated particles
known as extracellular vesicles. We propose that DNA can adsorb onto the surface of these particles to form a
“corona” that provides a target for anti-DNA antibodies. The significance of this research is the development of
well-controlled synthetic DNA-particles to address fundamental questions about the immunological properties of
particles that are not addressable with naturally occurring particles. The outcome of this research will be the
understanding of the mechanisms by which DNA binds to particles to form an antigenic substrate; the formation
of immune complexes by particles; the effects of surface DNA on the interaction of particles with immune cells;
and the role of surface DNA in immune stimulation. Aim 1 will determine the antigenicity of DNA adsorbed on
particles as a function of particle diameter, DNA length, and a protein corona using a previously developed
antibody binding assay as a readout. Aim 2 will use the antigenic particles identified in Aim 1 to elucidate the
immunostimulatory activity of DNA-particles in vitro, measuring the immune response and cellular internalization
of the DNA-particles. The development of a well-controlled synthetic particle system provides an innovative
approach to the study of SLE. Beyond SLE, the role of naturally occurring, cell-generated particles as elements
in disease pathogenesis has import...

## Key facts

- **NIH application ID:** 10880653
- **Project number:** 5R21AI175926-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** CHRISTINE K PAYNE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $197,170
- **Award type:** 5
- **Project period:** 2023-07-03 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880653

## Citation

> US National Institutes of Health, RePORTER application 10880653, Engineered DNA-particles to model immune events in systemic lupus erythematosus (5R21AI175926-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10880653. Licensed CC0.

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