Ionizable Lipid Nanoparticle Mediated mRNA Delivery to Multiple Myeloma Cells

Andres Hubsch

Students

Engineering and Applied Sciences

Faculty

Skirkanich Assistant Professor Of Innovation

Project Summary

Over the summer of 2021, I had the opportunity to work at the Mitchell Laboratory in the department of bioengineering at Penn. Dr. Michael Mitchell’s lab specializes in developing novel lipid nanoparticle systems for drug delivery. The lab utilizes knowledge of nano technology to build and test nanoparticles that can deliver cargo to specific cells. My project throughout the summer consisted of developing a system to deliver mRNA to multiple myeloma cells, with the overarching goal of contributing towards a tumor suppressor gene therapy for multiple myeloma cancer.

Multiple myeloma is a cancer formed from plasma cells that accumulate in the blood stream and bone marrow. Delivering mRNA tumor suppressor genes to multiple myeloma cells could prevent the formation of harmful tumors in these areas. To develop this delivery system, we first performed a screen of potential nanoparticle formulations with varying chemical structures. The screen revealed that particle formulation named A4 was effective at delivering mRNA to multiple myeloma cells cultured in lab. Furthermore, a screen for toxicity demonstrated a high rate of cell viability when compared to the control. Further experiments were then carried out to determine the optimal concentration of particles for a desired gene response.

Throughout the project, I learned how to design and carry out experiments in a wet lab, working with cell cultures, lipid nanoparticles, assays, and data analytics among other materials and methods. I learned to actively grow and manage cell cultures, including multiple myeloma and human bone marrow endothelial cells, as well as create lipid nanoparticles using a microfluidic device. I also learned to perform luciferase and toxicity assays during experiments, in addition to organizing and analyzing data results. All in all, my time working at the Michell Lab this summer has given me hands-on wet lab skills and a strong understanding of how to perform research, effectively supplementing my knowledge of bioengineering developed in the classroom.

To see my poster, visit Penn Presents: https://presentations.curf.upenn.edu/poster/ionizable-lipid-nanoparticle...