# Nonviral Topical Transfection with Calprotectin in Periodontitis

> **NIH NIH F32** · UNIVERSITY OF MINNESOTA · 2021 · $33,868

## Abstract

Abstract. Periodontitis is a highly prevalent condition characterized by a bacterial infection of periodontal
tissues. The development of improved, non-invasive treatments for periodontitis could have implications for
public health in the United States and worldwide. Calprotectin (S100A8/A9) is an antimicrobial protein that is
expressed in the cytoplasm of gingival epithelial cells and polymorphonuclear leukocytes. In a murine model of
periodontitis, S100A8/A9 slows the progression of periodontitis and reduces alveolar bone loss. We
hypothesize that efficient delivery and expression of calprotectin-specific mRNA in vivo will lead to reduced
inflammation and slow the progression of periodontitis. Herein, we propose a novel method to treat
periodontitis using topical delivery of an mRNA construct encoding calprotectin. We will demonstrate that food-
safe, polymeric gene delivery vehicles can topically deliver the therapeutic mRNA in vivo. To firmly establish
this approach, polyelectrolyte complexes (polyplexes) with mRNA will be characterized using dynamic light
scattering, zeta potential, and ethidium bromide (EtBr) dye exclusion. Optimization of polyplex uptake and
message translation will be quantified by expression of a GFP reporter gene using fluorescence microscopy
and flow cytometry. To increase biological persistence of the polyplexes complex and promote healing of
infected tissue, we will develop a cellulosic hydrogel bandage. The hydrogel will be characterized using
spinning disk rheology, and tensile testing. Polyplex loading into and release from the hydrogel will also be
quantified using fluorescence measurements or labeled polyplexes. Once ideal delivery conditions are
optimized, the effects of modified calprotectin expression will be assessed using a murine model for
periodontitis with and without endogenous calprotectin expression. The impact of calprotectin expression on
inflammation and alveolar bone loss will be quantified using flow cytometry and microCT measurements. Use
of the polyplex-loaded hydrogel bandages are expected to improve transfection efficiency, increase
calprotectin-dependent antimicrobial activity, and reduce the signs of experimental periodontitis in our mouse
model. If successful, this project has the capacity to provide clinicians with improved tools to treat periodontitis,
and improve understanding of topical gene delivery and the biology of periodontitis.

## Key facts

- **NIH application ID:** 10064626
- **Project number:** 5F32DE028174-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** William S Boyle
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,868
- **Award type:** 5
- **Project period:** 2018-12-03 → 2021-05-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064626

## Citation

> US National Institutes of Health, RePORTER application 10064626, Nonviral Topical Transfection with Calprotectin in Periodontitis (5F32DE028174-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10064626. Licensed CC0.

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