Publications

Anellovirus Structure Reveals a Mechanism for Immune Evasion

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Ring Therapeutics solved the first Anellovirus structure by using cryo-EM.

Anelloviruses are the principal constituent of the commensal human virome. However, their structure and features were not well studied and remain elusive. Here, Ring Therapeutics used cryo-EM to solve the first high-resolution structure for Anellovirus, which could not only help understand their interactions with the immune system but also provide a viral vector platform for gene therapy development.

To facilitate the symmetrical capsid assembly in the absence of viral genome, Ring Therapeutics designed LY1 ΔARM, an ORF1 construct wherein residues 2-45 are deleted. Negative stain TEM analysis of the LY1 ΔARM fragment showed the VLPs formed were more homogeneous and symmetric in morphology compared to full-length ORF1. 

Using the cryo-EM images collected at NanoImaging Services Inc., Ring Therapeutics determined the structure of the LY1 ΔARM particle to 3.98 Å resolution:

 

1)    The Anellovirus contained 60 copies of LY1 ΔARM fragments with icosahedral symmetry.

2)    Three individual domains were well resolved:  Jelly Roll (JR) domain, Spike P1 and P2 domains.

3)    JR domains form the core of the capsid, while spike P1 and P2 domains extending out from the capsid surface. Hypervariable region (HVR) of the spike P2 domain, located in the outmost of the capsid, might serve to aid in immune evasion.

4)    The structure of the LY1 Betatorquevirus can now be used to guide future anellovirus research as well as development of gene therapy vectors that elicit weak immune response.

Additional Publications

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CryoTEM in Preclinical Vaccine Development: Characterizing the lead candidate adjuvant formulation

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Negative Staining Electron Microscopy: Unfolding the structural arrangement of domains in single chain diabody

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Merck Used cryo-EM to Gain Insight Into Mechanism of Action by Imaging Structures of Inhibitory Antibodies Complexed with Arginase 1.

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Determine the Absolute Configuration of a New API Early in Drug Development with MicroED.

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Cryo-EM in Ligand Binding Site Studies: Sugar phosphate activation of the stress sensor eIF2B.

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