Abstract:
As a new class of medicines, mRNA platform has proven to be safe and effective. The objective of this study was to investigate the effect of local inflammation on platelet derived growth factor-BB (PDGF-BB) expression after gingival injection of PDGF-BB mRNA in lipid nanoparticles (LNPs) in ligature-induced rat periodontitis and to examine the dose-dependent effect of gingival delivery of mRNA. 3-0 silk was placed around maxillary left second molar for two weeks and removed, while the corresponding molar on the right was non-ligated. Under stereomicroscope, a significant bone loss at ligature sites was observed as compared to the non-ligature sites, indicating established periodontitis. However, there were no differences in inflammatory cytokine levels (IL-1β, TNF-α and IL-17a) and cellular infiltrates between the two sites. The local inflammation may occur at earlier time point in this ligature model. Different doses of PDGF-BB mRNA (low (3 µg), medium (10 µg), high (30 µg)), DPBS (control) and LNPs alone were injected into palatal gingiva upon ligature removal. After 24 hour of mRNA delivery, we found high levels of translated PDGF-BB protein at both ligature and non-ligature sites, demonstrating a trend of dose response. In addition, some amount of inflammatory cytokine including IL-1β, and IL-17a was detected. In conclusion, this study of 24 hour-local delivery of PDGF mRNA-LNPs into gingiva using ligature-induced rat periodontitis model results in high translated PDGF protein. Even though, local gingival inflammation was not detected in this established periodontitis model, this model may be useful for future testing of mRNA therapeutic effects.
