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US, UK Labs Propagate Rat ESCs; Stem Cell Sciences to Market Rat Models Using Tech

Stem Cell Sciences announced this week that two independent laboratories, one in the UK and one in the US, have successfully achieved germ-line transmission from rat embryonic stem cells using technologies licensed to SCS by Edinburgh University.
The scientific details of the work have been independently verified, and will be discussed in a paper to be published in a few months in a “major” peer-reviewed journal, an SCS official told CBA News this week.
He declined to say what labs conducted the work, however.
The company said that it believes this work marks the first time that rat germ-line transmission has ever been successfully demonstrated.
SCS also said that it now plans to engage in confidential discussions with interested parties seeking a sublicense to use rat ESCs in their commercial drug discovery programs.
“Although mouse embryonic stem cells and knock-out/knock-in mice have been around for a very long time, no one has achieved the same in rats” simply because rats have proven much more difficult than mice to use to generate ESCs that subsequently form chimeras with germ-line transmission, said Stem Cell Sciences CEO Alastair Riddell.
“I guess that is determined by the biology. Rats are different than mice, like monkeys are different than men. There are interspecies differences and technical complications,” Riddell said.
Under the terms of its agreement with Edinburgh University, SCS has exclusive rights to commercialize the rat ESCs, the specific medium used to generate and grow the cells, and the rats derived therefrom.
The company has licensed two patents covering this technology from the university. The culture medium patent family contains an MEK inhibitor, a GSK3 inhibitor and, alternatively, an FGF receptor antagonist that, when used in certain combinations, can be used to reliably grow rat ESCs in a serum-free environment.
The rat ESC patent family gives SCS the right to manufacture and commercialize unique rat models for biopharmaceutical research and drug development. According to SCS, this market has an estimated value of more than $80 million per year worldwide.
“As the exclusive licensees of that technology, we will be talking to companies that specialize in providing animals for pharmaceutical research,” said Riddell.
He added that it is difficult to speculate as to whether the rat ESCs and the knock-in/knock-out rats produced from them will be as widely used as their murine counterparts, “because we are still at a very early stage in this process.”  
Indeed, it will be some time before the knock-in/knock-out rats become commercially available. “But the technology is now ready for licensing. That is the whole point of this, really,” said Riddell.
Riddell said that knock-in and knock-out rats would be applicable to drug discovery in the area of target validation, much in the same way as knock-out and knock-in mice are used. The rats could also be used for toxicology, and to identify particular targets such as liver enzymes that may be adversely affected by a new drug. Or they could be used to understand the metabolism of a particular compound at a much earlier stage than clinical trials by inserting human liver enzyme genes into the rats.
This week’s announcement is the culmination of work that has been going on for more than a decade in the lab of Austin Smith at Edinburgh. “The next step, from my point of view as CEO, is to have discussions with various animal houses and determine the most optimal way of commercializing the IP,” said Riddell.
“From a scientific viewpoint, the next step is to create knock-out and knock-in rats based on this ESC technology.”

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