Sanford-Burnham Medical Research Institute said today it will use cellular selection and gene regulation technologies yet to be marketed by synthetic biotech company Intrexon, in a collaboration designed to accelerate human induced pluripotent stem cell (iPSC) research.
Intrexon may obtain commercial and intellectual property rights resulting from technological advances developed under the collaboration, in return for giving the research institute access to its Laser-Enabled Analysis and Processing (LEAP™) instrument and RheoSwitch Therapeutic System® (RTS).
The agreement is designed to aid Sanford-Burnham as it builds what it says will be the world’s largest collection of human iPSCs generated from individual patients and healthy volunteers.
LEAP is an automated system that provides high-throughput cell imaging coupled with laser-based cell processing. The instrument’s applications include rapid and accurate in situ purification of adherent cells and cell colonies, features that are particularly useful when working with complex human iPSC cultures.
“Intrexon’s LEAP instrument will allow us to isolate high-quality human iPSCs while eliminating non- or partially-reprogrammed cells or other undesirable cell types in the culture,” Yang Liu, Ph.D., manager of Sanford-Burnham’s Stem Cell Research Center, said in a statement.
RTS is a biological “switch” that enables inducible controlled gene expression by administering an activator ligand. RTA, will give Sanford-Burnham scientists a new method to regulate when certain genes are turned on or off in cells. The system also provides more accurate delivery of new therapeutic candidates to specific tissues in animal models.
“We’re interested in the RTS technology because it will help us to turn genes on or off in stem cells that have been transplanted,” Evan Y. Snyder, M.D., Ph.D., professor and director of Sanford-Burnham’s Stem Cell Research Center and Stem Cell and Regenerative Biology Program, said in a statement. “It can be used for therapeutic protein expression in stem cells that home to and help eradicate brain tumors.”
The Intrexon technologies comprise Sanford-Burnham’s latest effort to speed up iPSC development. A research team at the institute published results Sept. 25 in Nature Communications showing that kinase inhibitors added to starter cells helped generate many more iPSCs than the standard method, and much faster than the standard two weeks of transfection. The most potent inhibitors targeted three kinases—AurkA, P38, and IP3K—according to the study, which can be read here.
“In some cases, hESC-like colonies were obtained following as little as six days of transfection, although the yields were higher when transfection was continued for a few more days,” the study stated. “We have doubtless only scratched the surface in terms of the potential for technical improvements to RNA-based reprogramming.”
Tariq Rana, Ph.D., the study’s senior author and program director in Sanford-Burnham’s Sanford Children’s Health Research Center, explained the thinking behind the study to the research institute’s science blog, Beaker: “When you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier.”