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Lindsay Johnson

Predoctoral Fellowship in Drug Delivery, 2021 University of Texas Southwestern Medical Center

Elucidating the Tropism of Cell-Specific RNA Nanoparticles and Consequences for Anti-Cancer Efficacy


When the liver becomes injured or its cells are not functioning properly, it becomes inflamed and progresses towards disease and eventually cancer. A promising treatment approach is to use gene therapy, which requires the use of nanoparticles made up of chemical materials that work together to both carry and release a gene therapy to a targeted location. MicroRNA (miRNA) therapy is a promising approach that can directly inhibit oncogenes that drive cancer; however, the use of microRNAs as liver-cancer therapy has been challenged by unexpected nanoparticle-induced stimulation of immune cells, including Kupffer cells of the liver, resulting in adverse events. Clinical trial failures for miRNA therapy have illustrated the importance of understanding cell-level delivery of gene therapies. This project aims to understand cell-specific uptake of nanoparticles for gene therapy in the liver and develop the knowledge for creation of nanoparticles that enable liver cancer therapies to reach more patients. The project will focus on approaches to elucidate to which liver cell types our laboratory’s established nanoparticle formulations deliver RNA and explore anti-cancer efficacy. Currently, liver cancer patients have few options that only minimally extend survival. As cancer progresses, patients are no longer candidates for the current treatments due to their compromised liver function. If one is able to deliver the therapy to specific liver cells, this will help reduce toxicity and open up new treatment avenues. Completion of this project will help explain how the chemistry of nanoparticles affect their cell specificity within the liver and provide the necessary knowledge to advance the field of nanoparticle-based liver cancer therapy.

The PhRMA Foundation Predoctoral Fellowship support has helped fund my dissertation research and has helped me build confidence in my ability to succeed in a scientific career within the drug delivery field.

Lindsay Johnson

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