Tessera Therapeutics Aims to Rewrite DNA with New Age Gene Manipulators

By Ruchi Jhonsa, Ph.D.

Mobile genetic elements (MGEs) first discovered by Barbara McClintock in 1931 were considered junk and was later found to have functional significance. These DNA pieces famously known as jumping genes constitute nearly 50% of the human genome and carry the code for the machinery to either cut and paste or copy and paste themselves into a new site either within the host or into a nearby cell. While the relevance of these elements in the genome was obscure, recent work reveals that many organisms use MGEs for specialized functions, one that depends on its ability to move around the genome and modifying the DNA sequence in the process.

Making use of MGEs’ cut, copy and paste activity, a new age biotech company, Tessera Therapeutics is developing genetic manipulators that hold the potential to cure diseases that arise from errors in the genome while overcoming critical limitations of gene therapy and gene editors like CRISPR. The technology termed as ‘Gene Writing’ by von Maltzahn, CEO of the startup, uses modified MGEs to introduce small insertions and deletions or changes single or multiple base pairs in the genome. On July 7th, the company came out of hibernation after receiving over $50 million in funding and two years of research support from Flagship Pioneering for its gene writing technology.

“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.”

 

Changing the Paradigms

Tessera Therapeutics is an early-stage life sciences company that was founded by Geoffrey von Maltzahn, MIT-trained biological engineer, Jacob Rubens, an MIT trained synthetic biologist and other scientists at Flagship Labs in 2018 with an idea of creating a platform that could design, make, and launch gene writing medicines. The company holds a 30-person R&D team that has deep genetic medicine and startup expertise, including alumni from Editas, Intellia, Beam, Casebia, and Moderna.

“DNA codes for life. But sometimes our DNA is written improperly, driving an enormous variety of diseases,” says von Maltzahn “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.”

 

Workings of the Technology

Tessera’s gene writers are based on two different types of MGEs. One that can cut itself from its original location and integrate to a different location (transposons) and second, which can make its copy and transport the copy to a new location, creating a duplicate of itself (retrotransposons). Guarding the mobile elements are special sequences on either end that defines MGE’s boundaries. In between the boundaries are the genes for proteins that recognize these boundaries and cut them when transposon is moving out or copy them via an RNA intermediate into a new location.

Since its inception in 2018, Tessera has been searching genome sequences of thousands of bacterial species for these mobile genetic elements and modifying them to create new gene editors capable of producing any desired protein. Following this modification, MGE’s can be administered into desired tissue by lipid nanoparticles or AAV vectors, which will eventually cut or copy and paste protein-coding DNA pieces in any genomic location. 

So far, the company has identified around 6000 retrotransposons and 2000 transposons that show potential. Although it is yet to show potential in human studies, Tessera’s gene writers are already proving their worth in mouse models. The team has been able to show that MGE’s can insert large copies of the green fluorescent protein gene into the mouse genome.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: Codexis, Molecular Assemblies Enter Revolutionary DNA Synthesis Partnership

References
  1. https://www.tesseratherapeutics.com/news/flagship-pioneerings-scientists-invent-a-new-category-of-genome-engineering-technology-gene-writing

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