Cardiovascular assessment of lipid nanoparticle-encapsulating mRNA therapeutics in rats using telemetry and Star-Oddi logger devices

SPS 2023 -- Lipid nanoparticle (LNP)-encapsulating messenger RNA (mRNA)-based therapeutics and vaccines are an established and emerging drug modality for various indications. The global impact of SARS-CoV-2 mRNA vaccines during the coronavirus-19 pandemic demonstrated the value of mRNA-based platforms in preventing viral-induced serious illness, and several mRNA-based therapeutics are under investigation in clinical trials for chronic disease. Given that LNP delivery vehicles are comprised of novel lipid excipients and chronic medicines require repeat dosing via systemic administration, there is a need to assess the cardiovascular (CV) safety of the LNP components. Cardiovascular assessments are traditionally performed via telemetry implantation or external jacketed models. Star-Oddi data loggers are implanted subcutaneously for the collection of heart rate and body temperature. The benefits of data loggers compared to traditional implanted telemetry models are that the data loggers are less invasive, and still allow for continuous/uninterrupted heart rate and body temperature data collection. Use of data loggers may provide a minimally invasive option for investigation of mRNA-1944-related heart rate and body temperature changes in rats in place of nonhuman primates, supporting 3Rs goals in animal research.