A LEAP forward for stem cell research

LA JOLLA, Calif.—The Sanford-Burnham Medical ResearchInstitute, a world leader in stem cell research, has entered into acollaboration agreement with leading synthetic biology company Intrexon Corp.The partnership will focus on rapidly accelerating induced pluripotent stemcell research by giving world-class researchers access to innovative,proprietary technology platforms that are not widely available.

The agreement grants Sanford-Burnham access to Intrexon'sLaser-Enabled Analysis and Processing (LEAP) instrument and RheoSwitch TherapeuticSystem (RTS). These sophisticated cellular selection and gene regulationtechnologies, respectively, are proprietary to Intrexon and are not currentlyavailable on the market. In exchange, according to the terms of the agreement,Intrexon may gain commercial and intellectual property rights resulting fromtechnological advances made under the auspices of the collaboration.

Induced pluripotent stem cells (iPSCs) are stem cellsderived from adult rather than embryonic cells. Sanford-Burnham is currently buildingthe largest collection of iPSCs in the world from individual patients andvolunteers.

The LEAP instrument is Intrexon's proprietary automatedsystem that provides high-throughput cell imaging and processing. Theinstrument images cells right in their plates, where computational software isable to identify cell types based on their shape and chemistry. Undesired celltypes can be targeted and eliminated insitu by way of a laser system.

"The laser fires 1,000 shots per second to eliminate undesirablecells without touching cells of interest," says Dr. Fred Koller, vice presidentof business development at Intrexon and co-inventor of the LEAP instrument. "Wehave the only technology today that's able to purify adherent cells directly inthe dish."

The LEAP instrument will allow greater efficiency of iPSCcultures, and will allow cell lines to be developed much more quickly. Standardmethods typically require two plates to generate one cell line.

"The bottleneck for progress has been how many colonies youcan generate with limited technicians," says Dr. Yang Liu, manager of the StemCell Research Institute at Sanford-Burnham. "Thanks to this collaboration, wewill have access to software that will enable high-throughput plates—allowingthe possibility of multiple cell lines on a single plate."

Using the LEAP instrument to develop iPSCs promises a vastlyimproved method because researchers will have no need to take cells out of thewell.

"This will allow us to save reagents, while also reducing therisk of contaminations," says Liu.

The LEAP instrument will help researchers to achieve thenext step in stem cell development, which is cell differentiation. The typicalprocess of transitioning iPSCs into a desired cell type has about a 10-percentefficiency rate, resulting in an impure culture that contains roughly 10 partsthe desired cell type and 90 parts something else. The laser-based processingaffording by the LEAP instrument will allow researchers to purify the cellsdirectly in the adherent state, yielding a sample containing only the desiredcell type.

"If we can achieve this, we can create and label a puresample of a desired cell type," says Liu. This is especially exciting for theprospect of growing pure pancreatic and liver cells, among others.

The agreement also provides Sanford-Burnham access toIntrexon's RTS technology, a proprietary ligand-activated biological "switch"that allows researchers to turn gene expression on or off. This will allowSanford-Burnham scientists to regulate when certain genes are expressed incells, which has several promising applications with regard to iPSCs.

"We're interested in the RTS technology because it will helpus to turn genes on or off in stem cells that have been transplanted," Dr. EvanY. Snyder, director of Sanford-Burnham's Stem Cell Research Center and StemCell and Regenerative Biology Program, said in a media release about theagreement. "For example, it can be used for therapeutic protein expression instem cells that home to and help eradicate brain tumors."

Sanford-Burnham is a nonprofit medical research institutewith locations in California and Florida. It consistently ranks among the topfive organizations in the world for its scientific impact in the fields ofbiology and biochemistry. Sanford-Burnham's Stem Cell Research Center,nicknamed the "Stem Cell Core," provides its resources and services toresearchers at nonprofit and for-profit organizations around the world.Sanford-Burnham and its partners are pursuing iPSCs for a variety ofprospective uses, including drug development or potentially using culture-borncells to treat disease directly.

Intrexon is a privately held biotechnology company focusedon the industrial engineering of synthetic biology.

"We're a private company that's trying to get biotech intonew spaces beyond healthcare and agriculture—into animal sciences and theenergy sector, for example," says Koller. "Here, we're engaging in a differentmarket, and iPSCs are something we believe in. There are technical hurdles toovercome yet, but we think our technology will be enabling in the effort tocreate the next wave of therapies."