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CAMBRIDGE, Mass.—Seeking to replace traditionalreprogramming methods with targeted genome engineering, Cellectis bioresearch,a subsidiary of the Cellectis Group and a genome-engineering specialist, haspartnered with Stemgent Inc., a developer of cellular reprogramming tools forleading stem cell researchers worldwide.
 
 
Both companies have developed extensive experience in stemcells—namely, induced pluripotent stem (iPS) cells. Under an agreementannounced March 7, the companies will equip stem cell researchers with toolsthat generate genome-engineered iPS cells for use in their research andregenerative medicine by marrying Cellectis' genome engineering expertise withStemgent's work in cellular reprogramming.
 
 
Cellectis developed a high-throughput synthesis platformthat is capable of synthetizing thousands of such molecules each year: TALEN,which uses synthetic molecules made of a fusion of an engineered transcriptionfactor and an endonuclease. TALEN masters specifity issues to avoid off-targeteffects and toxicity, and enables researchers to overcome epigeneticmodification, like cytosine methylation, that usually abolishes binding andcleavage.
 
 
"In addition to the perfect match between the two companies'technologies, the management team from both sides share the same vision on theway of developing future applications using iPS cells," says Jean-CharlesEpinat, deputy CEO of Cellectis. "Generating 'clean' iPS cells is aprerequisite for clinical applications involving iPS cells, and thus allclinical applications in regenerative medicine will benefit from thistechnology."
 
 
While traditional reprogramming methods can lead to the integrationof unwanted genetic material into the host genome, disrupting a reprogrammedcell's function, Stemgent's proprietary mRNA reprogramming technology addressesthe challenges around deriving non-viral, non-integrating, clinically relevantiPS cells for use in regenerative medicine, drug discovery and basic research,says Dr. James Kehler, director of global services at Stemgent.
 
"We wanted to go beyond the ability to recruit and reprogrampatient samples of interest," says Kehler. "We thought there would be a realneed for a group to validate drug targets or introduce precise genomicmodifications for an iPS line. This partnership struck us as a very rapid wayof doing precise genetic studies and a pragmatic approach to working withestablished leaders in the field."
 
 
Stemgent's technology will be integrated into Cellectis' iPSHub reprogramming platform. The end result will be a "one-stop shop" forpatient/donor biopsies to be used for iPS cells by academic and pharma/biotechcustomers, says Epinat.
 
 
"No doubt, in the near future, drug testing will be heavilybased on iPS cells," he says. "Cellectis is already offering, for instance,human cardiomyocytes and hepatocytes for drug-toxicity applications and lookingto develop additional products for drug screening and testing that reflect thephysiopathology of diseases. Regenerative medicine applications are the naturalextension, and Cellectis is building capacities first in generatingclinical-grade iPS cell lines, which are the starting materials for any futureclinical studies."
 
"I do believe that while in the longer term, regenerativetherapies using iPS cells will come to the clinic in a global context, the moreready achievement will be the development of new assays utilizing iPS-derivedcells from a range of patients who can add value early in the screening processto help identify off-target toxicities," Kehler concludes.
 
 
 

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