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Start-Up Licensing Flexible Genome-Editing Technology

DNA molecules

DNA molecule display (Christian Guthier, Flickr)

31 March 2017. A start-up biotechnology company is licensing techniques from two universities that make genome editing more flexible and better control gene expression. Financial aspects of the agreements between Canopy Biosciences LLC in St. Louis, with Washington University in St. Louis and Johns Hopkins University in Baltimore were not disclosed.

Canopy was formed in 2016 to take a technology to market that adapts emerging Crispr-Cas9 genome editing techniques for better control of the extent of gene expression needed for therapeutics. Crispr, short for clustered regularly interspaced short palindromic repeats, is based on bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA. The actual editing of genomes with Crispr in most cases uses an enzyme known as Crispr-associated protein 9 or Cas9. RNA molecules guide the editing enzymes to specific genes needing repair, making it possible to address root causes of many diseases.

Up to now, Crispr could entirely knock-out defective genes to remove mutations responsible for disease, but not control the proteins expressed by those defects. Canopy’s technology, however, makes it possible to use genome-editing for situations where completely removing a gene would cause adverse effects. That technology quickly and reliably produces hypomorphic mutations, or genetic alterations that reduce gene expression, on demand, dialing down the extent of proteins transcribed by the gene.

These more regulated mutations are accomplished by adding adenosine nucleotides, components of RNA responsible for energy metabolism in cells, called polyA tracks in Canopy’s technology. PolyA tracks act as control units for genes, with the size of polyA tracks added to a gene in DNA controlling the extent of gene expression and protein production. A research team led by cell biologist Sergej Djuranovic at Washington University demonstrated production and control of hypomorphic mutations using polyA tracks with DNA from 5 model organisms, including E. coli bacteria and fruit flies, as well as human cells in lab cultures, in a paper published in January 2017 appearing in the journal Nature Communications.

The research by Djuranovic and co-author Rachel Green at Johns Hopkins University is the basis of the license from the 2 institutions. Canopy is marketing the technology under the brand name TUNR Flexible Gene Editing System, for 3 types of adjustable gene editing for therapies. The company also established prices for the services, ranging from $1,990 to $4,990.

Canopy’s president Edward Weinstein believes the TUNR system can be useful in situations such as cancer immunotherapy where better control of gene expression may be needed. “Previously, researchers have only been able to completely delete, or ‘knockout’, a particular gene,” says Weinstein in a company statement. “With TUNR, we can dial in the exact level of expression necessary, such as 10, 25, or 75 percent. This has become particularly important for new immuno-oncology drug targets like PDL1, which has a range of expression in cancer patients and is used to predict their responsiveness to the latest promising cancer drugs.”

The company was formed in 2016 and is being incubated at BioGenerator, a life sciences investor and accelerator in St. Louis. In December 2016, Canopy received $2 million in financing from BioGenerator and other angel investors.

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