Creative Biostructure

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Cryo-EM for Gene Therapy

Creative Biostructure is a world leading service provider specialized in transmission electron microscopy (TEM) analysis of gene therapy and drug delivery particles. Unlike crystallography approaches, Cryo-EM does not require crystallization step, and allows direct visualization of biomolecules with minimal sample preparation. This makes Cryo-EM a powerful tool for structural characterization. We offer a complete GMP-compliant TEM analysis platform that includes both negative stain TEM and Cryo-TEM technology. With these advanced tools, we provide professional one-stop services from method development, sample preparation, data collection, data analysis and structural interpretation.

As a critical step of gene therapy, Cryo-EM has been used as a powerful tool for structural characterization of viruses. The two adenoviruses species, C adenoviruses and D adenoviruses, share the same shell-like core. However by using Cryo-EM, researchers found that they have very different surface structures, called decorations or loops, which are key to this virus’ behavior. It is their surface structure that determines which receptors on human cells the virus bind to. Therefore, the distinct surface structures of adenoviruses can help targeted delivery of virus and can be applied in development of vaccines in gene therapies.

Overall structure and organization of the major and minor capsid proteins in HAdV-D26. Figure 1. Overall structure and organization of the major and minor capsid proteins in HAdV-D26.

Based on our EM platform, our analysis package includes but not limited to:

  • General morphology
  • Level of aggregation
  • Size distribution
  • Circularity
  • Packaging
  • Lamellarity
  • Membrane thickness
  • Protein localization

Our experts will tailor the analysis and generate a detailed report for your specific project:

  • Representative EM-images
  • Quantitative analysis
  • Concluding summary with comments from the expert team

Creative Biostructure offers a complete EM analysis package that includes both negative stain transmission electron microscopy and cryo-transmission electron microscopy. Each of these methods provides powerful image datasets that leads to high resolution structural determination of biomolecules. Please contact us for more information.

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References:

  1. Yong Zi Tan, Sriram Aiyer, et al. Sub-2 Å Ewald curvature corrected structure of an AAV2 capsid variant. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-06076-6.
  2. Xiaodi Yu, David Veesler, et al. Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses. Science Advances 10 May 2017: Vol. 3, no. 5, e1602670. DOI: 10.1126/sciadv.1602670