Charles River Laboratories International Inc. and ATEM Structural Discovery (ATEM) have formed a strategic partnership to provide clients access to ATEM’s cryo-electron microscopy (cryo-EM) service solutions. Cryo-EM is a technique that determines the 3D structures of proteins and is utilized to identify how proteins function, how they malfunction in disease and the most effective way to target them with therapies.
 
ATEM’s platform integrates highly optimized biochemistry, hardware, and software to provide in-depth structural insights about challenging targets at a commercial scale. ATEM’s technology directly images vitrified biological macromolecules in single-particle experiments at high resolution. Subsequently, reconstructed coulomb potential maps then allow the precise modeling of 3D atomic coordinates that elucidate the target structure. This leads to the identification of novel distinct binding sites and significantly improves the discovery of drug candidates.
 

Optimizing Candidate Selection

By combining ATEM’s cryo-EM expertise with Charles River’s end-to-end capabilities, the alliance has the potential to significantly accelerate drug discovery efforts from hit design through to lead optimization. With early insights into how lead candidates interact with their intended disease target, clients can interpret actual structural changes, allowing more informed prioritization and optimization of lead candidates.
 
Through the collaboration, Charles River clients will have access to ATEM’s platform to support their drug discovery efforts. When utilizing ATEM’s cryo-EM platform, clients will be provided with enhanced insights into challenging targets by viewing the 3D structure of full biochemical assemblies, ligand-bound complexes and biologic drugs. This partnership allows Charles River to enhance drug discovery projects by enabling structure-based design for a greater portfolio of targets.
 

AAV Capsid Ratio Analysis and mRNA Formulation Development in Support of Gene Therapies

Cryo-EM has become a powerful orthogonal tool to support both quality control and research and development (R&D) efforts in adeno-associated virus (AAV) vector-based gene therapies (i.e. full/empty capsid ratio analysis), as well as novel mRNA and plasmid-based drugs. By utilizing technologies including analytical ultracentrifugation (AUC), capillary isoelectric focusing (cIEF), transmission electron microscopy (TEM), and cryo-EM, clients can expect to receive qualitative and quantitative data to ensure improved dosing accuracy. Additionally, cryo-EM allows the use of minimal amounts of sample, fast turn-around times, and improved statistical accuracy.
 
For recombinant protein drugs, ATEM’s models will provide fast track virus particle analysis as part of the adventitious agent testing on cell banks and bulk harvest samples, along with support for the development and optimization of downstream purification efforts through rapid TEM-based impurity screening and visualization.
 
“We’re very excited to offer ATEM’s cryo-EM platform to our clients. By expanding our technology services through strategic partnerships, we’re able to nimbly assess and meet our client’s needs, while providing innovative solutions to accelerate their drug discovery and development,” commented Birgit Girshick, corporate executive vice president, Discovery and Safety Assessment and Biologics Solutions, Charles River
 
“ATEM offers deep and leading technical expertise, which combined with Charles River’s market reach will help us to serve a rapidly growing market need,” added Dr. Karl Bertram, founder of ATEM Structural Discovery.