mRNA technology has emerged as a powerful new approach for cancer treatment by teaching the immune system to recognize and attack tumors. However, one major limitation remains: current delivery systems cannot control which cells receive the mRNA. As a result, many unintended cell types can produce the therapeutic proteins, reducing effectiveness and increasing side effects.

Dr. Brown’s research aims to solve this problem by developing highly targeted mRNA delivery systems that direct treatments to the immune cells needed to fight cancer while preventing unwanted activity in other tissues.

He and his team will combine two innovative technologies to this end. The first uses short genetic sequences that function like molecular “off switches,” preventing mRNA activity in certain cell types. The second uses specially engineered antibodies to guide mRNA-containing lipid nanoparticles directly to selected immune cells.

Early studies have shown promising results: reducing mRNA activity in liver cells improved anti-tumor immune responses while lowering liver-related toxicity. Dr. Brown will build a library of targeted mRNA delivery systems and test their ability to improve cancer vaccines and immune cell therapies, including CAR T-cell treatments, in both blood cancers and solid tumors. If successful, this work could lead to safer and more effective mRNA-based immunotherapies with greater precision, stronger anti-cancer responses, and fewer side effects.

Projects and Grants

Targeting RNA-LNP to boost cancer vaccine immunity

Identifying genetic determinants of tumor immune composition by spatial functional genomics
Technology Impact Award | 2020

Development of a novel technology for cancer immunology target discovery
Technology Impact Award | 2018