CAMBRIDGE, Mass. — Ring Therapeutics, a Flagship Pioneering Company, today published a major new analysis of anelloviruses, a large and diverse family of commensal viruses that have co-evolved with humans over time – which may provide a new approach to gene therapy. The research appears in the August 11, 2021 issue of the scientific journal Cell Host & Microbe. Like the many different types of bacteria in the human microbiome, commensal anelloviruses are a major part of the human virome, although until now, the true breadth and depth of anellovirus diversity was a mystery.
While previous research demonstrated that anelloviruses are plentiful in the body, limitations in technology have made it challenging to characterize their genetic diversity and the role they play in human health. Using a new method of detecting and identifying unique anelloviruses, called the Anelloscope™, researchers at Ring nearly tripled the number of known anellovirus gene sequences, representing thousands of new entities that could serve as a library of novel viral vectors and potential gene therapy candidates. The researchers were also able to track certain subtypes of anelloviruses for long periods of time, indicating that they persist without being cleared by the immune system.
"What we uncovered is a tremendous leap forward for Ring's therapeutic development strategy," said Tuyen Ong, M.D., Co-author of the paper and Chief Executive Officer at Ring Therapeutics. "Anelloviruses seem to have the ability to persist without triggering an immune response or causing harm in the human body. This opens a world of opportunities to create a completely new class of novel viral vectors that can address an expansive range of diseases."
Most People are Naturally Carrying Anelloviruses
The Ring Therapeutics researchers and their collaborators from Harvard Medical School, Scripps Research Translational Institute, and the Gothenburg Global Biodiversity Centre, conducted the study by analyzing blood specimens from transfusion donors and recipients across five time points: before transfusion, and four after transfusion. This allowed the researchers to characterize the native anelloviruses present in both groups and how the transfusion recipients' anellovirus composition changed over several months following an infusion of donor blood. They determined that people may carry several – and up to one hundred – similar but related types of anelloviruses, and that blood transfusions can alter or add to it without impacting the human host. Some of the anelloviruses are long-lasting and were detected as long as 260 days following the infusions.
"More than five years ago, we asked the question - what if there were a human commensal virome that could be harnessed to create a new category of medicine," said Co-author Avak Kahvejian, Ph.D., Co-Founder and Chairman of the Board, Ring Therapeutics, and General Partner, Flagship Pioneering. "In order to answer this larger question, we needed to find evidence of its existence, persistence, and transmission. We set out to do this by looking at blood transfusions in a rigorous and systematic way that led to realization of the vast number of anelloviruses."
"This spurred us to look at anelloviruses in a way no one has before, going deeper into their genetic makeup and the ways in which they interact in the body," said Nathan Yozwiak, Ph.D., Senior Author of the paper and Senior Director, Viral Genomics, Ring Therapeutics. "With this research, we wanted to understand more about the true nature, complexity, and prevalence of anelloviruses, and we found that each anellovirus sequence represents a distinct type of outer shell ("capsid") that could potentially encase and deliver a therapeutic gene or nucleic acid (such as RNA) to the human body. The newfound diversity of anelloviruses means that there are thousands of potential vectors for delivering gene therapy payloads."
The First Disruption in More Than 50 Years
Ring has created a novel vector Anellogy™ platform to harness the unique properties of anelloviruses – the first true disruption in the gene therapy space in more than 50 years. With the proprietary platform combined with the growing body of research on the vast number of anelloviruses, Ring is building a robust pipeline of redosable vectors compatible with the human immune system to target specific tissues. The Anellogy™ platform includes Anellovectors™, which the company believes can be engineered for a broad spectrum of therapeutic modalities and delivered through multiple routes of administration.
About Ring Therapeutics
Founded by Flagship Pioneering in 2017, Ring is driving a new paradigm in gene therapy and nucleic acid medicines by harnessing the human commensal virome. The company has developed a unique combination of expertise across virology, genomic epidemiology, structural and cell biology. In just two years, Ring has already identified thousands of anelloviruses, and has created Anellovectors – engineered vectors consisting of single-stranded DNA rings that, once administered, will remain as episomes in the nucleus. Ring is now pursuing a clinical development strategy for advancing several applications of Anellovectors to therapeutics programs.
About Flagship Pioneering
Flagship Pioneering conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability. Since its launch in 2000, the firm has, through its Flagship Labs unit, applied its unique hypothesis-driven innovation process to originate and foster more than 100 scientific ventures, resulting in over $90 billion in aggregate value. To date, Flagship has deployed over $2.4 billion in capital toward the founding and growth of its pioneering companies alongside more than $19 billion of follow-on investments from other institutions.