Powering a New Era of Gene Therapy

Our Anellogy platform leverages the human commensal virome to deliver redosable and targetable gene therapy unlike any that have come before.

How It Works

Flagship Pioneering asked: What if the human commensal virome could be harnessed to create therapeutics?

The Commensal Virome

We uncovered a large family of diverse viruses called anelloviruses, that constitute the majority of the human commensal virome. Anelloviruses are stealthy, inhabiting numerous tissue types without triggering the immune system’s alarm. Once inside the cell, the viral genome remains as a stable episomal element, a single-stranded ring of DNA adjacent to our own genome. Anelloviruses have coevolved with us over millennia, yielding a symbiotic relationship never before described in humans. We believe the virome, an intrinsic element of biology that is present in virtually every person and a diverse array of tissues represents an opportunity to create a robust gene therapy platform.

Anellovectors

We harness the commensal virome with the creation of Anellovectors

Engineered vectors consisting of single-stranded DNA rings that, once administered, will remain as episomes in the nucleus. They have the rare potential to be harmless, transferring DNA to new cells in a variety of tissue types without damaging tissues or activating the immune system.

Revolutionizing Gene Therapy

Using our proprietary Anelloscope discovery platform, we uncovered and characterized the world’s largest collection of commensal viruses and are harnessing those best suited for specifically targeting a wide array of diseases.

Key Features of Anellovectors

Redosable

Gene therapy faces a major barrier: the inability to redose. The generation of antibodies against treatment results in a robust immune response to any subsequent exposure. This means that every cell must be reached with the initial dose if the therapy is to be effective. The commensal virome is ubiquitous within the human body and does not trigger any significant immune reactions. Therefore, our Anellovectors have the potential to treat patients with pre-existing immunologic barriers and/or those requiring redosing.

Tropism with Cellular
and Tissue Specificity

Many tissue types are elusive to current gene therapy vectors and are currently unreachable. A vector that is both redosable and able to target unreachable tissues has the potential to open solutions for a host of genetic diseases. Our platform promises to target a broad array of tissue specificities benefitting from the inherent diversity of tissue tropism by leveraging the commensal virome.

Lack of Insertional Mutagenesis

Current virus-based gene therapy platforms can randomly integrate within the human genome, disrupting the function of important genes. Anellovector cargo remain as episomes in the nucleus and do not affect the genome. This eliminates the potential risk of insertional mutagenesis, making for a safer form of gene therapy.

Versatile

Our Anellovectors can be engineered to accommodate a wide variety of therapeutic modalities and can be delivered via multiple routes of administration.

Scalable

We are developing an in-house proprietary capability called AnelloBricks™ to rapidly scale manufacturing and explore the broad therapeutic potential of various Anellovectors. By implementing state-of-the-art manufacturing, we plan to scale production to commercial levels and take the Anellovector platform from bench to bedside.

Building the Future

For many years, effective gene therapy has been limited by an inability to redose, weak tissue tropism, and poor tolerability. Our novel approach has the potential to revolutionize the field and unlock the full potential of gene therapy. We aim to expand the applications of genetic medicine beyond gene replacement, opening up a wide array of modalities and mechanisms.

Origins

We started by investigating the human commensal virome at Flagship Labs, Flagship Pioneering’s innovation foundry. Through this exploration, the founding Flagship team, composed of Avak Kahvejian, PhD; Erica Weinstein, PhD; and Noubar Afeyan, PhD, uncovered a family of viruses that we identified in transfusion samples around the turn of the century but were largely dismissed after they were deemed non-pathogenic. The team surmised that the natural history of the virus in transfusion medicine could serve as compelling evidence of its safety, ubiquity, and transmissibility. The team founded a ProtoCo (prototype company), FL46, Inc., and embarked on the exciting project of mining genomic data for deeper viral discovery and “vectorizing” these viruses through synthesis and engineering. After experimental demonstrations were successfully completed and they substantiated the potential for a broad new gene therapy platform, Flagship Pioneering launched Ring Therapeutics, Inc. as a NewCo in 2017.

About Flagship Pioneering

Flagship Pioneering conceives, creates, resources, and develops first-in-category life sciences companies to transform human health and sustainability. Since its launch in 2000, the firm has applied a unique hypothesis-driven innovation process to originate and foster more than 100 scientific ventures, resulting in over $30 billion in aggregate value. To date, Flagship is backed by more than $3.3 billion of aggregate capital commitments, of which over $1.9 billion has been deployed toward the founding and growth of its pioneering companies alongside more than $10 billion of follow-on investments from other institutions. The current Flagship ecosystem comprises 39 transformative companies, including Axcella Health, (NASDAQ: AXLA), (NASDAQ: DNLI), Evelo Biosciences (NASDAQ: EVLO), Foghorn Therapeutics, Indigo Agriculture, Kaleido Biosciences (NASDAQ: KLDO), Moderna Therapeutics (NASDAQ: MRNA), Rubius Therapeutics (NASDAQ: RUBY), Seres Therapeutics (NASDAQ: MCRB), and Syros Pharmaceuticals (NASDAQ: SYRS).

To learn more about Flagship Pioneering, please visit:
www.FlagshipPioneering.com

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