Lipid Nanoparticle Mediated mRNA Delivery for Applications in Immunotherapy

Benjamin Nachod, SEAS ’26, Clarksburg, MD

My name is Ben Nachod, and I’m a rising sophomore studying Bioengineering, pursuing minors in Chemistry and Engineering Entrepreneurship. This summer I worked under the guidance of Dr. Michael Mitchell, a professor of Bioengineering here at Penn, and Ajay Thatte, a PhD student studying Bioengineering. Our lab’s research lies at the interface of drug delivery, cellular and molecular bioengineering and biomaterials science, with the goal of therapeutically targeting biological barriers. 

I worked on two main projects this summer, with the first centering around the use of lipid nanoparticles (LNPs) for ex vivo engineering of primary CD4+ T cells for autoimmunity applications. In this project, we transfected primary human T cells with Foxp3 mRNA to induce expression of the Foxp3 marker with the goal of modulating immune cell function. We were able to successfully induce Foxp3+ T-cells that were found to suppress proliferation of T effector cells ex vivo. These results were promising and provide a framework for potential future work into applications of using Foxp3 engineered T-cells into in vivo autoimmunity disease models.

The second project I worked on investigated the co-delivery of dimethyl acetamide (DMA) alongside lipid nanoparticles as means of mediating inflammation caused by delivery. Inflammation caused by LNP-mediated delivery serves as a serious barrier to many treatment options, including mRNA therapeutics. Being able to downregulate this response would be incredibly valuable and allow for more unconfined development of novel therapeutic approaches in the future. This project is still ongoing and I’m excited to return to the Mitchell lab this fall to continue this research.

Throughout the summer I learned how to form lipid nanoparticles, perform flow cytometry, and run enzyme-linked immunosorbent assays (ELISAs), skills that I will continue to use for the foreseeable future. I was able to independently plan and perform different assays and tests, learning how to adapt protocols for our experiments and keep an accurate record of procedure in my lab journal. When me and my mentor first began to design the DMA project, we had to read countless amounts of previous literature to understand the best path to take. It was really cool to be able to learn and navigate the entirety of the research process. Every step of the way is calculated and there are countless factors to consider when planning an experiment and executing it. 

Dr. Mitchell, alongside Ajay and the other graduate students/postdocs in my lab served as valuable mentors to me. Talking to them and learning about their paths gave me the chance to further develop my own career aspirations and widen my viewpoint surrounding the fields of immunology and drug delivery. This summer experience solidified my goal of pursuing a research focused career, one where I’ll utilize principles of bioengineering and biomaterials science to develop new therapeutic technologies for human health applications. This opportunity would not have been possible without the generous support of Penn Career Services.

This is part of a series of posts by recipients of the 2023 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here

By Career Services
Career Services