Daniel Estabrook
Senior Advisor, Bioproduct Research & Development Eli Lilly & Co.
I am currently a research scientist at Eli Lilly and Company in Boston, MA focusing on the development of next-generation genetic medicines, including the delivery and formulation challenges that underlie them. During my time at Lilly, I have primarily worked on the formulation optimization of both RNA-lipid nanoparticles and nucleic acid therapeutics. As this seminar will demonstrate, this work has included both solution phase siRNA-LNPs, as well as frozen mRNA-LNPs. Prior to this, I worked as a graduate student at the University of California, Los Angeles, where I developed stimuli-responsive polymeric surfactants for perfluorocarbon nanoemulsion delivery. I am continually motivated by the use of organic chemistry to address structure-property relationships in the nanoparticle-mediated drug delivery.
Seminars
- A novel mechanism for lipid tail oxidation is shown to produce degradants that react with neighbouring cargoes to form RNA-lipid adducts
- Mildly acidic, histidine-containing buffers are shown to shut down this degradation pathway and improve siRNA-LNP stability for months at room temperature
- An understanding of how buffer attributes (identity, molarity, and pH) impact mRNA-LNP structure, morphology, and transfection efficiency enables rational design of frozen storage buffers
