Characterization and Control of Dynamic Rearrangement in a Self-Assembled Antibody Carrier.

Biomacromolecules
Anshul DhankherJulie A Champion

Abstract

Thorough characterization of protein assemblies is required for the control of structure and robust performance in any given application, especially for the safety and stability of protein therapeutics. Here, we report the use of multiple, orthogonal characterization techniques to enable control over the structure of a multivalent antibody carrier for future use in drug delivery applications. The carrier, known as Hex, contains six antibody binding domains that bind the Fc region of antibodies. Using size exclusion chromatography, analytical ultracentrifugation, and dynamic light scattering, we identified the stoichiometry of assembled Hex-antibody complexes and observed changes in the stoichiometry of nanocarriers when incubated at higher temperatures over time. The characterization data informed the modification of Hex to achieve tighter control over the protein assembly structure for future therapeutic applications. This work demonstrates the importance of using orthogonal characterization techniques and observing protein assembly in different conditions over time to fully understand and control structure and dynamics.

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Citations

Oct 17, 2020·Nanomedicine : Nanotechnology, Biology, and Medicine·Wei Lv, Julie A Champion
Aug 21, 2021·Bioconjugate Chemistry·Christopher J AddonizioMatthew J Webber

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