Sigma Life Science reports that its SAGE Labs initiative has successfully used its CompoZr® Zinc Finger Nuclease (ZFN) technology to generate knockin rats. SAGE Labs will use this technology to produce off-the-shelf rat models for use in the study of human diseases as well as custom models for customers.
Sigma Life Science says that, in a proof of concept study, a copy of the green fluorescent protein (GFP) was inserted in a targeted fashion into the multidrug-resistance gene Mdr1a of a rat. The firm already offers an Mdr1a knockout model, which shows total loss of P-glycoprotein protein via Western blot, accumulation of substrate drugs in the brain, decreased drug elimination, susceptibility to irritable bowel disease, and albinism.
In October 2009, Sigma Aldrich launched SAGEspeed™ to develop and provide genetically engineered knockout rodent animal models within four to five months for use in drug R&D. Knockin models will now also be supplied.
The technology and methodology employed by SAGEspeed reduces the cycle time that it takes to create knockout mouse models using conventional embryonic stem cell-based technologies by around two-thirds, according to Sigma Aldrich.
ZFNs are a class of engineered DNA-binding proteins that facilitate targeted editing of the genome by creating double-strand breaks in DNA at user-specified locations. With well-established and robust protocols, these cellular processes can be harnessed to generate precisely targeted genomic edits resulting in cell lines including somatic cell lines with targeted gene deletions, integrations, or modifications.