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Cellectis, Wyss Inst. Partner on Recoding Human Genome

DNA puzzle

(Arek Socha, Pixabay)

1 May 2018. A bioengineering center at Harvard University and a biotechnology company are creating a process for genetically editing human cell lines to produce synthetic virus-resistant proteins for research and therapies. The collaboration between the Wyss Institute for Biologically Inspired Engineering at Harvard in Cambridge, Massachusetts and biotechnology enterprise Cellectis in New York and Paris was announced today at the Genome Project-write 2018 Scientific Working Meeting in Boston.

Cellectis is a developer of immunotherapies to treat cancer, but also offers a basic genome editing service called Talen, short for transcription activator-like effector nucleases. Talens are synthetic enzymes designed for genome engineering that Cellectis says provides highly precise editing of genomes. In addition, Talens enzymes can be deployed across the human genome and configured to make multiple edits at one time, a process known as multiplexing.

In their collaboration called the Recode project, Cellectis and Wyss Institute researchers are applying Talen technology to edit human genomes to produce cells that resist infections from viruses and other microbes. A team led by Harvard geneticist George Church, one of the Wyss Institute’s core faculty and principle investigator on the Recode project, earlier recoded the genome of E. coli bacteria — a common model microbe in labs, as well as a cause of food poisoning — to remove redundant components in its DNA. These redundant elements are expressed as codons, sequences of three DNA molecules that correspond to specific amino acids in the production of proteins. As reported by Science & Enterprise, Church and colleagues succeeded in identifying 7 codons in the E. coli genome as redundant, as well as some 62,00 instances where they occur.

In further work, Church and colleagues recoded the E. coli genome to remove a single codon, but a key component that enables the microbe to become resistant to most viruses and designed to live only in lab environments, not in the wild. Researchers on the project now want to take that concept further, to human cells. The Wyss-Cellectis team expects to use Talens enzymes to modify codons at some 400,000 locations across parts of the human genome where proteins are coded, removing redundant codons.

By removing redundant codons, the researchers expect to produce cell lines that cannot be taken over by viruses, which need the full repertoire of codons to cause infections. In a joint statement, Church notes that “the Recode project aims to create ultra-safe human cells that are resistant to infection with all viruses and prions.” Prions are infectious agents made of protein material often associated with neurodegenerative disorders such as Creutzfeldt-Jakob disease. He adds that the cells and associated technologies being generated will “enable more effective ways to manufacture protein therapeutics, vaccines, cell therapies, and transplantable organs.”

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