Flagship Pioneering's Scientists Invent a New Category of Genome Engineering Technology: Gene Writing

CAMBRIDGE, Mass., July 7, 2020 /PRNewswire/ -- Flagship Pioneering today announced the unveiling of Tessera Therapeutics, Inc. a new company with the mission of curing disease by writing in the code of life. Tessera is pioneering Gene Writing™, a new biotechnology that writes therapeutic messages into the genome to treat diseases at their source.

Tessera's Gene Writing platform is a potentially revolutionary breakthrough for genetic medicine that addresses key limitations of gene therapy and gene editing. Gene Writing technology can alter the genome by efficiently inserting genes and exons (parts of genes), introducing small insertions and deletions, or changing single or multiple DNA base pairs. The technology could enable cures for diseases that arise from errors in the genome, including monogenic disorders. It could also allow precise gene regulation in other diseases such as neurodegenerative diseases, autoimmune disorders, and metabolic diseases.

"While profound advancements in genetic medicine over the last two decades had therapeutic promise for many previously untreatable diseases, the intrinsic properties of existing gene therapy and editing have significant shortcomings that limit their benefits to patients," says Noubar Afeyan, Ph.D., founder and CEO of Flagship Pioneering and Chairman of Tessera Therapeutics. "Our scientists have invented a new technology, called Gene Writing, that has the ability to write therapeutic messages into the genomes of somatic cells. We created Tessera to pioneer its applications for medicine. However, the breakthrough is broad and could be applied to many different genomes from humans to plants to microorganisms."

A New Era of Genetic Medicine

Geoffrey von Maltzahn, Ph.D., an MIT-trained biological engineer; Jacob Rubens, Ph.D., an MIT-trained synthetic biologist; and other scientists at Flagship Labs, the enterprise's innovation foundry, co-founded Tessera in 2018 to create a platform that could design, make, and launch Gene Writing medicines. A General Partner at Flagship Pioneering, von Maltzahn has co-founded numerous biotechnology companies, including Sana Biotechnology, Indigo Agriculture, Kaleido Biosciences, Seres Therapeutics, and Axcella Health.

"DNA codes for life. But sometimes our DNA is written improperly, driving an enormous variety of diseases," says von Maltzahn, Tessera's Chief Executive Officer. "We started Tessera Therapeutics with a simple question: 'What if Nature evolved a better solution than CRISPR for inserting curative therapeutic messages into the genome?' It turns out that engineered and synthetic mobile genetic elements offer the potential to go beyond the limitations of gene editing technologies and allow Gene Writing. Our outstanding team of scientists is focused on bringing the vast promise of this new technology category to patients."

Mobile genetic elements, the inspiration for Gene Writing, are evolution's greatest genomic architect. The first mobile genetic element was discovered by Barbara McClintock, who won the 1983 Nobel Prize for revealing the mobile nature of genes. Mobile genetic elements code for the machinery to move or copy themselves into a new location in the genome, and they have been selected over billions of years to autonomously and efficiently "write" their DNA into new genomic sites. Today, mobile genetic elements are among the most abundant and ubiquitous genes in nature.

Over the past two years, Tessera has been mining genomes to discover novel mobile genetic elements and engineering them to create Gene Writing technology. Tessera's Gene Writers write therapeutic messages into the genome using RNA or DNA templates. RNA-based Gene Writing uses an RNA template and Gene Writer protein to either write a new gene into the genome or guide the rewriting of a pre-existing genomic sequence to make a small substitution, insertion, or deletion. DNA-based Gene Writing uses a DNA template to write a new gene into the genome.

By harnessing the biology of mobile genetic elements, Gene Writing holds the potential to overcome the limitations of current genetic medicine approaches by:

• Efficiently writing small and large alterations to the genome of somatic cells with minimal reliance upon host DNA repair pathways, unlike nuclease-based gene editing technologies.
• Permanently adding new DNA to dividing cells, unlike AAV-based gene therapy technologies.
• Writing new DNA sequences into the genome by delivering only RNA.
• Allowing repeated administration of treatments to patients in order to dose genetic medicines to effect, which is not possible with current gene therapies.

Tessera has licensed Flagship Pioneering's intellectual property estate, which was begun in 2018 with seminal patent filings supporting both RNA and DNA Gene Writing technologies.

Tessera's Scientific Advisory Board includes Luigi Naldini, David Schaffer, Andrew Scharenberg, Nancy Craig, George Church, Jonathan Weissman, and John Moran, who collectively have decades of experience in developing gene therapies and gene editing technologies, and also have commercial expertise from 4D, UniQure, Casebia, Cellectis, Magenta, and Editas. Tessera's Board of Directors includes John Mendlein, Flagship Executive Partner and former CEO of multiple companies; Melissa Moore, Chair of Tessera's Scientific Advisory Board, Chief Scientific Officer of Moderna, member of the National Academy of Sciences, and founding co-director of the RNA Therapeutics Institute; Geoffrey von Maltzahn; and Noubar Afeyan. The 30-person R&D team at Tessera has deep genetic medicine and startup expertise, including alumni from Editas, Intellia, Beam, Casebia, and Moderna.

About Tessera Therapeutics
Tessera Therapeutics is an early-stage life sciences company pioneering Gene Writing™, a new biotechnology designed to offer scientists and doctors the ability to write and rewrite small and large therapeutic messages into the genome, thereby curing diseases at their source. Gene Writing holds the potential to become a new category in genetic medicine, building upon recent breakthroughs in gene therapy and gene editing, while eliminating important limitations in their reach, utilization and efficacy. Tessera Therapeutics was founded by Flagship Pioneering, a life sciences innovation enterprise that conceives, resources, and develops first-in-class category companies to transform human health and sustainability.

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 $34 billion in aggregate value. To date, Flagship is backed by more than $4.4 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 41 transformative companies, including Axcella Health (NASDAQ: AXLA), Denali Therapeutics (NASDAQ: DNLI), Evelo Biosciences (NASDAQ: EVLO), Foghorn Therapeutics, Indigo Ag, Kaleido Biosciences (NASDAQ: KLDO), Moderna (NASDAQ: MRNA), Rubius Therapeutics (NASDAQ: RUBY), Sana Biotechnology, Seres Therapeutics (NASDAQ: MCRB), and Syros Pharmaceuticals (NASDAQ: SYRS).

SOURCE Flagship Pioneering