Connor A. Brandenburg, M.S. – Takeda Pharmaceutical Company

Please tell us about your background: where you grew up, studied, and why you chose the field you did.

I’m a California native! I was born and raised in the Sacramento area, and in 2015, I moved to San Diego. During my undergraduate journey at Point Loma Nazarene University (PLNU), I joined Prof. Katherine Maloney’s lab, studying natural products isolation, structure elucidation, and synthesis. I enjoyed using chemistry to help understand biological problems. I then went on to an internship in the small molecule and peptide drug discovery group at Takeda Pharmaceutical Co. after my undergraduate work concluded. This experience inspired me to dig deeper into biopharmaceutical research and led me to pursue an M.S. in Chemistry from UC San Diego (2022), where I contributed to chemical glycobiology research programs in Prof. Kamil Godula’s group. As a budding synthetic organic chemist and chemical biologist, I learned about the wonders of bioconjugation to build multipartite biomacromolecules and facilitate targeted drug delivery.

What does your current position entail? How does it tie into your previous experience, and where is it going?

I am currently a Senior Research Associate in the Oligonucleotide Chemistry & Delivery group within the Research arm of Takeda. My role focuses on the bioconjugation of oligos (siRNA and ASO) to delivery vehicles (mAbs, Ab fragments, lipids, and other motifs) to accelerate our preclinical drug discovery efforts across our core neuroscience, GI/liver/inflammation, and oncology therapeutic areas of focus. I’m excited about the future of targeted RNAi therapeutics to realize treatments for “difficult to drug” diseases and can’t wait to see how patients’ lives are changed by these medicines.

In what context did you first learn about light scattering and Wyatt Technology's instruments? How has your Wyatt instrumentation contributed to your research and development studies?

As a protein-nucleic acid hybrid material, antibody-oligonucleotide conjugates (AOCs) have unique biophysical properties that are unlike anything else that I’ve worked with. While the pendant oligo absorbs UV radiation strongly at 260 nm, the protein component absorbs at 280 nm, complicating analysis by UV-vis spectrophotometry. They’re highly net negatively charged thanks to the 20 to 40 negative charges contributed by the oligo. Like any biologic, they can form high-molecular weight aggregates which are not easy to investigate via traditional modes of analysis like mass spectrometry. My team needed a tool to better understand how our AOCs behaved under native, high salt conditions—and liquid chromatography coupled to multi-angle light scattering (LC-MALS) detection was the answer! This instrument helps us characterize AOC stability in different formulation conditions and understand trends in species’ aggregation and fragmentation as we explore different conjugation chemistries.