Evaluation of transfection efficacy, biodistribution, and toxicity of Branched Amphiphilic Peptide Capsules (BAPCs) associated with mRNA.

Description:
Nanoparticles (NPs) have shown to be a suitable mRNA delivery platform by protecting mRNA against ribonucleases and facilitating cellular uptake. Several NPs have shown great success in delivering mRNA intranasally, intratracheally, and intramuscularly, though intravenous mRNA delivery has been somewhat less explored. Only few NPs have been tested for systemic delivery of mRNA, and the vast majority are formulated with polyethylene glycol (PEG). The incorporation of PEG presents a few trade-offs: PEGylated nanoparticles can prevent early clearance by the mononuclear phagocytic system (MPS), thus increasing retention in the body which may increase therapeutic effects. On the other hand, it has been reported that treating patients with PEGylated drugs can result in production of anti-PEG antibodies, which will accelerate blood clearance and trigger hypersensitivity. Consequently, it is desirable to have alternative PEG-free delivery methods for mRNA to avoid these inconveniences. Our research group developed BAPCs (branched amphiphilic peptide capsules), a peptide-based nanoparticle that resists disruption by chaotropes, proteases, and temperature, thus displaying significant stability and shelf-life. In this study, we demonstrated that similarly to PEG, mRNA shields the BAPC cationic surface to avoid early clearance by the MPS. Multispectral optoacoustic tomography (MSOT) an fluorescence reflectance imaging were used to analyze the biodistribution within the MPS organs. Additionally, BAPCs enhance intracellular delivery of mRNA with negligible cytotoxicity or oxidative stress. These results might pave the way for future therapeutic applications of BAPCs as a delivery platform for systemic mRNA. Additionally, BAPCs are easier to formulate, meaning a large-scale production of this nanoparticle is feasible for potential preclinical and clinical studies.

Speaker: Adriana Avila Flores - Auburn University
I am currently an Assistant Professor in the Department of Biological Sciences at Auburn University. My laboratory investigates new delivery platforms for nucleic acids. I obtained my B.S. in Chemistry from the Autonomous University of Madrid (Madrid, Spain) and M.S. in Industrial Chemistry from the Basque Country University (Bilbao, Spain). Afterward, I worked two years for a Biotechnology company in Bilbao, Spain. In 2010, I joined the Biochemistry and Molecular Biophysics department at Kansas State University to pursue my Ph.D. degree. After three years of postdoctoral stays at Kansas State and Auburn University, I started my tenure-track position in Biological Sciences in 2017.