Anastasis Biosensor CaspaseTracker rtTA – C15014 Unmet NeedAnastasis, Greek for "rising to life", is a newly discovered cell recovery phenomenon by which a cell undergoes reversal of apoptosis or programmed cell death. Research has shown that even cells that exhibit the hallmarks of late-stage cell death such as activation of executioner caspases are able to undergo anastasis. Anastasis can be a mechanism of tumorigenesis and recurrence, mediating cancer cell survival during treatment. Conversely, anastasis may also mitigate tissue damage by protecting cells that would be difficult to recover, such as cardiomyocytes, neurons and photoreceptor cells. Therefore, suppression and activation of anastasis could be critical therapeutic targets in cancer and regenerative medicine, respectively.
Being able to track cells after they have undergone anastasis is critical to the development of therapeutics that either activate or suppress this survival mechanism. However, it is technically challenging to detect and track anastasis
in vivo because the cells that have reversed the cell death process can be morphologically indistinguishable from normal healthy cells. The primary method of tracking anastasis
in vivo is labelling cells with activated (cleaved) caspases using immunostaining or caspase biosensors. However, activated caspases and these current cleavage-activated biosensors are degraded shortly after anastasis, making these methods unable to track the fate of cells, especially in long term, once the cells have recovered from cell death process.
Technology OverviewThe inventors have developed a novel caspase biosensor, the mammalian version of
in vivo CaspaseTracker biosensor, which is able to permanently label cells undergoing anastasis, enabling the long-term track of the fate of anastatic cells in live animals. Importantly, this invention could be used for drug screening of intractable diseases mediated by anastasis with patient-derived xenografts and patient-derived tumor organoids.
The CaspaseTracker biosensor is also able to detect and track non-apoptotic caspase activity, which plays potential roles in diverse normal cell functions, such as regulation of neuronal activity, learning and memory, spermatid individualization, microRNA processing, cell proliferation, and cell fate patterning. Therefore, this CaspaseTracker biosensor can also facilitate these studies
in vivo.
Stage of DevelopmentThis invention has been shown to identify and permanently label cells recovered from caspase activation in mammalian cells
.PublicationsJ Vis Exp. 2018 Feb 1;(132)