Tessera Therapeutics Partners with Cystic Fibrosis Foundation to Treat Life-Threatening Disease with Gene Writers

On November 3rd, Flagship’s Tessera Therapeutics announced entering a treatment-focused collaboration with the Cystic Fibrosis Foundation. This partnership is part of a larger collaboration involving Flagship’s Pioneering Medicines, for which the Cystic Fibrosis Foundation is committing up to $110 million.

This first-of-its-kind strategic alliance aims to develop therapeutics that address the unmet needs of people living with cystic fibrosis by leveraging the innovations and teams of multiple Flagship-founded companies.

“The collaboration of Pioneering Medicines and the Cystic Fibrosis Foundation will support the development of Gene Writers designed to give people living with cystic fibrosis functional CFTR genes, with the goal of restoring normal, healthy lung function,” said Paul Biondi, President, Pioneering Medicines and Executive Partner, Flagship Pioneering.

“Gene Writers have the potential to revolutionize the treatment of cystic fibrosis and to deliver multiple new medicines that introduce a full-length CFTR sequence, or to make true corrections of pathogenic alleles in the CFTR sequence.”

Gene Writing Technology to Combat Cystic Fibrosis

Founded by Geoffrey von Maltzahn, an MIT-trained biological engineer, Jacob Rubens, an MIT-trained synthetic biologist, and other scientists at Flagship Labs, Tessera Therapeutics launched with the idea of creating a platform that could design, make, and launch gene writing medicines.

The Boston-based startup uses mobile genetic elements (MGEs), first discovered by Barbara McClintock in 1931, to develop genetic manipulators with huge potential. The technology called ‘Gene Writing’ uses modified MGEs to introduce small insertions and deletions or changes to single or multiple base pairs in the genome.

For the collaboration with the Cystic Fibrosis Foundation, Tessera’s lead Gene Writers will use target-primed reverse transcription (TPRT), which evolved in a class of MGEs known as retrotransposons. These MGEs use DNA-binding, DNA-nicking (without double-strand breaks to DNA), and reverse transcription to make an alteration.

Cystic fibrosis (CF) is a life-threatening genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in the production of a dysfunctional protein. The CFTR protein is necessary to attract water to the surface of cells, without which the mucus in the lungs clogs the airway and traps bacteria. As a result, patients with CF suffer from infections, inflammation, respiratory failure, and progressive lung damage that have life-shortening consequences.

Tessera’s Gene Writers will aim to make true corrections of specific mutations, such as the F508-del mutation, which drives roughly 70% of CF cases, as well as other nonsense mutations, and to introduce a functional full-length copy of the CFTR gene at its endogenous locus. Tessera and Pioneering Medicines will advance the technology through preclinical development and prepare it for first-in-human proof of concept studies.

“The Cystic Fibrosis Foundation’s extensive network of scientists, companies and clinicians knowledgeable about cystic fibrosis will help accelerate screening and development of our cystic fibrosis-targeting Gene Writers. We hope our collaboration leads to treatments and cures for cystic fibrosis,” said Geoffrey von Maltzahn, Co-Founder and CEO of Tessera.

Advantages Over Other Methods

“CRISPR is a phenomenal method for programmable cutting of the genome. In nature, it evolved to destroy invasive DNA, and it is a great tool for turning something off. However, in cystic fibrosis, we want to fix the gene with a three-nucleotide insertion that has to be performed with high efficiency and fidelity or make individual mutations in the minority of patient populations in different locations. Nucleases are not good at doing either of those. Base editors, on the other hand, can make single nucleotide changes with the caveat that they are good at transition mutations but not transversions,” Geoffrey von Maltzahn told GeneOnline.

“The ability of Tessera’s Gene Writers to write free nucleotides with very high efficiency and make single-nucleotide transition and transversion modifications without bystander mutations is a big advantage. The Gene Writers are delivered as therapeutics comprised of RNA molecules within lipid nanoparticles, offering the potential for scalable, re-dosable genetic medicines,” he added.

Author

Rajaneesh K. Gopinath