Live-Cell based assay for DNA Damage Response

New Market Opportunity
Cell-based assays play a decisive role in the current drug screening process, yielding safer drugs in a cost effective manner. Such assays offer the potential to screen out compound failure earlier in the discovery and development lifecycle, delivering increased productivity. Globally, the total cell-based assay market is expected to rise to $720 million by 2009 with a CAGR of approximately 10% over the next 5 years.

Background
Cell-based assays are screening procedures that have the ability to track the behaviour of the dynamic activities inside a cell. With automation imperative, these processes catalyse the lead identification process with a faster turn around time. The drug discovery industry is adopting a cell-based assay approach as such assays reflect the biological dynamic activity inside the organism better than the in vivo animal models. Engineering the right cell line and cultivating them for the specific target is a critical task along with understanding the biological behaviour of the target.

Technology Description
The NUI, Galway Cell-based assay enables monitoring of DNA damage responses in living cells. This assay also allows the potential for high-content target identification screening for 1. Genes involved in DNA damage responses and 2. Drugs/Chemicals that cause DNA damage.

The assay uses quantitation of the centrosome by microscopy as a means to:

1.Detect DNA damage in living cells.

2.Screen for agents acting on the DNA damage response pathways that involve CHK1.

The assay detects centrosome amplification after DNA damage in a time- and dose-dependent manner and employs inhibition of a key kinase by RNAi, pharmacological agents or gene targeting to suppress DNA damage-induced centrosome amplification.

Principal Investigator: Dr Ciaran Morrison, NUI, Galway.

Competitive Advantage

1. Suited to automated screening of centrosome number and allows the quantitative analysis of DNA damage responses in individual living cells.

2. The live cell based assay represents a ‘high content screen’. Off-target responses that potentially impair the utility of the drug or candidate gene as a target for further development can be monitored in real time.

3. Applicable to a wide range of DNA damaging agents including ionising radiation, radiomimetic drugs, topoisomerase II inhibitors and cell cycle arresting drugs, all of which are used in current cancer therapies.

4. Identification of key targets in anticancer drug development.

5. Screen for testing of DNA-damaging drugs, alone or in conjunction with extant anticancer agents (combination chemotherapy).

6. Platform for screening multiple genes or drugs.

7. Model system for high content screening.

IP status and references
A priority patent application encompassing the assay and its applications has been filed (2006).
1, DNA damage induces Chk1-dependent centrosome amplification. Bourke et al., EMBO Reports 2007
2, Involvement of Centrosome Amplification in Radiation-Induced Mitotic Catastrophe Dodson et al., Cell Cycle 2007

Type of Business Sought
NUI, Galway are interested in entering into licensing agreements and/or collaborative partnerships.

Type of Offer: Licensing



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