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PRESENTER INFORMATION

ABSTRACT

mRNA vaccines have emerged as a breakthrough technology in the COVID-19 pandemic. While mRNA can express any desired signal by encoding the nucleotide sequence, there are also other types of RNA (e.g., siRNA, mRNA, repRNA) with varying functions that may be harnessed for therapeutic applications. But in order to develop an effective RNA therapeutic, we must also be able to deliver these molecules into target-specific regions in our body. To this end, nanoparticles have emerged as versatile tools, but the optimal RNA delivery platform for specific tissues and cells remains a question that needs addressing for successful clinical translation. Tackling this challenge requires deep considerations at the interface of materials and biology, where one must identify biological barriers that hinder RNA delivery and engineer novel strategies to overcome the bottlenecks. Thus, in this seminar, I will introduce two approaches I have developed for next-generation RNA therapeutics. The first is a materials science-based approach, where the delivery nanoparticle was designed to: (1) mass load and protect the RNA cargo; (2) selectively accumulate in target-specific cell types in the body; and (3) deliver the RNA directly to the cell cytoplasm to improve delivery efficiency, bypassing traditional cellular uptake pathways. The second takes a biological approach. Here, we discovered that a key innate immune pathway actively inhibits certain RNA vaccines, and then rationally designed a next-generation vaccine to suppress this innate response for dramatically improved vaccine-elicited antigen-specific immune response. These works highlight the importance of integrating materials science and biology, particularly at their interface, to create effective and impactful solutions to the in vivo drug delivery challenge.