title: Real-time observation of protein aggregates in pharmaceutical formulations using liquid cell electron microscopy.
abstract: Understanding the properties of protein-based therapeutics is a common goal of biologists and physicians. Technical barriers in the direct observation of small proteins or therapeutic agents can limit our knowledge of how they function in solution and in the body. Electron microscopy (EM) imaging performed in a liquid environment permits us to peer into the active world of cells and molecules at the nanoscale. Here, we employ liquid cell EM to directly visualize a protein-based therapeutic in its native conformation and aggregate state in a time-resolved manner. In combination with quantitative analyses, information from this work contributes new molecular insights toward understanding the behaviours of immunotherapies in a solution state that mimics the human body.
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: DiMemmo
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016, USA. debkelly@vt.edu debkelly@vt.edu.
authors.forename: A
authors.initials: A
authors.lastname: Cameron Varano
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Haulenbeek
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016, USA. debkelly@vt.edu debkelly@vt.edu.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016, USA. debkelly@vt.edu debkelly@vt.edu.
authors.forename: Kaya
authors.initials: K
authors.lastname: Patel
authors.affiliation: Application Science, Protochips, Inc, Raleigh, NC 27606, USA.
authors.forename: Madeline J
authors.initials: MJ
authors.lastname: Dukes
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA.
authors.forename: Songyan
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Hubert
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Piccoli
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA 24016, USA. debkelly@vt.edu debkelly@vt.edu.
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Kelly
mesh_terms: D004339:Drug Compounding; D016898:Interferon-alpha / Q000737:chemistry / Q000627:therapeutic use; D008854:Microscopy, Electron / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry; D066329:Protein Aggregates; D011487:Protein Conformation; D013997:Time Factors
chemical_list: D016898:Interferon-alpha; D066329:Protein Aggregates; D011092:Polyethylene Glycols