BUSINESS OPPORTUNITY
We have developed a cell line that simultaneously reports on the three arms of the Unfolded Protein Response (UPR). These three evolutionarily conserved signaling arms are activated through the endoplasmic reticulum (ER)-resident IRE1α, PERK and ATF6 where they alleviate stress due to unfolded protein accumulation. When these arms are dysregulated, they are involved in different diseases such as cancer, neurodegenerative disease, obesity, and diabetes. Therefore, there is a large effort to identify UPR regulators for potential therapies.
None of the currently available research tools reports simultaneously and judiciously, in real time, on the activation of the three UPR arms. Scientists at University of Oslo have now developed a stable triple-color fluorescence reporter cell line for monitoring (UPRL-3). The utility of the UPRL-3 cells was validated in a small-scale small-molecule library screen. The cell-line can be used to screen for and characterize molecules that modulate specific UPR arms. In addition, new molecules developed for other targets could be screened for potential off-target effects of this key signaling pathway that is affected by a variety of external stimuli.
We are currently seeking industrial partners for collaborations on this technology and for licensing.
TECHNOLOGY DESCRIPTION
The UPRL-3 cell line was made using CRISPR-Cas9 knock-in in HEK293T cells, resulting in detection of IRE1α arm activation by XBP1s-GFP, PERK arm activation by ATF4-RFP, and the ATF6 arm by ATF6-BFP. We have confirmed that UPRL-3 can robustly and sensitively detect specific activation of the different arms after ER stress induction using two chemical UPR inducers, thapsigargin (TG) and tunicamycin (TM).
Using UPRL-3 cells we have analyzed a small library of known FDA approved oncology drugs and demonstrated which branches of the UPR are activated.
We are currently in the process of developing a triple 22Rv1 prostate cancer reporter cell line (double reporter is ready).
Intellectual property and publication plans
A patent application is planned based on the manuscript describing the development, characterization, and validation of the cells, to be submitted for publication shortly.
