2022, July 6
Ring Therapeutics Publishes the First Human Anellovirus Structure with Key Insights on Its Assembly, Function and Immune Evasion Properties
Cambridge, Mass. – July 6, 2022 – Ring Therapeutics, a life sciences company founded by Flagship Pioneering to revolutionize programmable medicines with its commensal virome platform, today announced a pre-print publication in bioRxiv featuring the first anellovirus structure identified from a synthetically produced human anellovirus capsid protein. The capsid structure suggests a steric hindrance mechanism for successful immune evasion by anelloviruses. These discoveries serve as a key pillar of Ring’s AnellogyTM platform in harnessing the unique structure and biology of commensal anelloviruses to engineer the next generation of potentially redosable programmable viral vectors.
“Anelloviruses coevolved with us for millennia and constitute the majority of the human commensal virome, so much so that they seem to be accepted by our immune system as part of us. We believe we’ve uncovered one important mechanism by which they may be keeping the immune system at bay,” said Tuyen Ong, MD, MBA, Chief Executive Officer at Ring. “Building on genomic predictions from our extensive database of diverse anellovirus sequences, our team experimentally identified the anellovirus capsid protein, ORF1. Through expression of this protein, we were able to decipher that the capsid structure of anelloviruses comprised a jell-roll core that supports a novel crown structure hypothesized to prevent, via steric hindrance, the binding of antibodies. Insight from this structural work provides a potential mechanism for anellovirus immune evasion and will help guide the design of our next-generation viral vectors, AnelloVector™ therapeutics, to usher in a new future of programmable medicines.”
In the publication, researchers experimentally validated the predicted anellovirus capsid protein, ORF1, and produced the first structure of a human anellovirus particle. ORF1 was expressed in insect cells and assembled into viral particles ~32 nm in diameter, consistent with estimates of naturally isolated anelloviruses. The anellovirus particle is composed of 60 ORF1 fragments with a modified jelly roll domain core architecture and residues that extend from the surface to form a novel elongated surface structure where hypervariable regions lie at the apex. Five surface proteins pack together in a ringed structure resembling a crown. At the apex of the crown is a domain formed by the hypervariable region that is hypothesized to sterically hinder antibody binding to key ORF1 motifs. This potential steric hindrance could prevent antibody recognition and neutralization of the virus and allow anelloviruses to repeatedly infect humans while successfully evading the immune system. Altogether, this publication strengthens the potential of Ring’s AnellogyTM platform in harnessing the unique anellovirus structure to generate a new class of viral vectors that could successfully evade the immune system, overcoming one of the major hurdles facing gene therapy today.
About Ring Therapeutics
Ring Therapeutics is revolutionizing the gene therapy and nucleic acid medicine space by harnessing the most abundant and diverse member of the human commensal virome, anelloviruses. The company developed the Anellogy™ platform which focuses on anelloviruses to potentially treat a broad range of diseases. Through harnessing the unique properties of these commensal viruses, the Anellogy™ platform generates diverse vectors that exhibit both tissue-specific tropism and the potential to be redosed. Partnered with Flagship Pioneering, Ring Therapeutics aims to develop and further expand its portfolio through leveraging its platform to unlock the full potential of gene therapy and nucleic acid medicines, enabling a variety of mechanisms that successfully deliver therapeutic cargo to unreachable organs and tissues. To learn more, visit https://live-ringtx.pantheonsite.io or follow us on Twitter at @Ring_tx.
Ring Therapeutics Media
Brittany Leigh, PhD