Embryonic Stem Cells for HTS
Invitrogen (www.invitrogen.com) is currently developing a platform for rapidly engineering human and mouse embryonic stem cells for use in screening. “This platform consists of a toolbox of genetic elements that can be rapidly assembled and integrated into the stem cell genome at specific loci,” said Jon Chesnut, director, stem cells and regenerative medicine.
“Cell screening platforms can be created with lineage- and tissue-specific promoters driving reporter genes as well as with gene perturbation and overexpression constructs.”
These platforms could then be used for screening compounds in stem cells or in cell populations differentiated from the stem cells. The tangible, near-term goal is to use these platforms in drug screening to provide more relevant tissues and compounds.
The aim of Chesnut’s group is to provide relevant platforms for driving screening that would allow companies to do their screening in human, normal adult tissue rather than primary or cadaveric cells. “We want to be able to either fail drugs for safety reasons sooner or get those compounds that can be applied to market sooner,” said Chesnut.
“This is the future of the business; testing on transformed cells simply doesn’t work the same way. Moving toward working with stem cell-derived adult-human cells should reduce the necessity of using whole-animal models, lowering the development cost of a drug as well as the time to market.”
Ryan McGuinness from MDS Analytical Technologies, formerly MDS Sciex (www.mdssciex.com), presided over a roundtable discussion about the strong points of competing label-free assays.
“Label-free cell-based platforms, with their abilities to monitor receptor activation in a native setting, further the push toward biorelevant and disease relevant screening in a manner that is easy for the user to set up, straightforward to perform, and provides results in rich, real-time manner. The early adopters, mostly big pharma, have seen the advantages of these technologies in bringing more biorelevance into the drug discovery pipeline earlier.” said McGuinness.
“Label-free technologies are still in their early stages, and the feedback we have gotten from our early adopters has been crucial. The collaborative effort is key.”