Invention by ESE Professors obtains licensing by NGI
| April 20, 2006 | |
| An invention, Real-time Assay for the Detection of PARP Activation, by Jun Nakamura and James A. Swenberg was recently licensed by the National Genetics Institute (a subsidiary of Laboratory Corporation of America). This invention was previously approved a US patent in 2005. The Executive Summary is included below.Executive Summary of Invention: Real-time Assay for the Detection of PARP Activation
Background: DNA single strand breaks (SSBs) are one of the most frequent lesions in genomic DNA generated either by oxidative stress or during DNA repair pathways. Existing technologies for measuring SSBs are time-consuming and use harsh chemicals which can create artifactual induction of SSBs. Invention in Brief: UNC has established a new real-time assay to assess an imbalance of DNA SSB repair by indirectly measuring activation of poly(ADP-ribose) polymerase, or PARP one of the DNA repair proteins by monitoring intracellular NAD(P)H depletion. It can detect PARP activation in living cells in 30-240 minutes without cell lysis. The assay is performed in 96-well plates using a standard plate reader. Since the assay does not require DNA extraction or alkaline treatment, it is unlikely to cause artifactual induction of SSBs, and can be more sensitive than the current state of the art (single cell gel electrophoresis). Advantages ” Uses existing lab equipment to achieve superior results ” Real-time detection of PARP activation and SSBs in intact cells ” Data within 4 hours (versus 2-4 days with current state of the art) ” Superior sensitivity and reproducibility (cv: 10%) ” Slight modification to assay allows user to distinguish whether SSBs are repaired via base excision repair. ” Low sample requirements (<500,000 cells) Research Uses ” Screen compounds for genotoxicity and PARP inhibition ” Screen chemicals that specifically inhibit DNA repair enzymes ” Screen human populations for diminished capacity for SSBs or base excision repair. Licensing and Patent Status: US patent was approved (7/2005). Exclusive licensing was contracted (3/2006). Inventors: Jun Nakamura and James A. Swenberg. Related Publication: Nakamura, J., Asakura, S., Hester, S.D., de Murcia, G., Caldecott, K. W., and Swenberg, J. A. Quantitation of intracellular NAD(P)H in living cells can monitor an accumulation of DNA single strand breaks in real time. Nucleic Acids Res., 31: e104, 2003. Takanami, T., Nakamura, J., Kubota, Y., and Horiuchi, S. The Arg280His polymorphism in X-ray cross-complementing gene 1 impairs DNA repair ability. Mutat Res. 582:135-145, 2005. Lin, C.H., Leow, H.T., Huang, S.C., Nakamura, J., Swenberg, J.A., and Lin, P.H. Induction of cytotoxicity, aldehydic DNA lesions, and poly(ADP-ribose) polymerase-1 activation by catechol derivatives of pentachlorophenol in calf thymus DNA and in human breast cancer cells. Chem Res Toxicol. 18:257-264. 2005. Lin, P.H., Pan, W.C., Kang, Y.W., Chen, Y.L., Lin, C.H., Lee, M.C., Chou, Y.H., and Nakamura, J. Effects of naphthalene quinonoids on the induction of oxidative DNA damage and cytotoxicity in calf thymus DNA and in human cultured cells. Chem Res Toxicol. 18:1262-1270. 2005. Pachkowski, B.F., Winkel, S., Kubota, Y., Swenberg, J.A., Millikan, R.C., and Nakamura, J. XRCC1 genotype and breast cancer: Functional studies and epidemiologic data demonstrate interactions between XRCC1 codon 280 His and smoking. Cancer Res. 66:2860-2868. 2006. Dantzer, F., Ame, J.C., Schreiber, V., Nakamura, J., Menissier-de Murcia, J., and de Murcia, G. Poly(ADP-ribose) Polymerase-1 Activation During DNA Damage and Repair. Methods Enzymol. 2006 (in press). For further information please contact Rebecca Riggsbee Lloyd by email at Rebecca_Lloyd@unc.edu |
