Patent ID: 9611514
Date: 2017-04-04
CPC Classifications: A61K,A61P,C12N,C12Q,G01N

Claim:
1. A method for measuring a DIS3 PIN domain endonuclease activity inhibitor that induces a synthetic lethality in a cancer cell having a mutation in a hDIS3 RNB domain, comprising: a) constructing a model system comprising DIS3, or a DIS3 fragment, wherein the DIS3fragment comprises a RNB domain comprising at least 80% identity to a sequence AA 427-843of SEQ ID NO: 1 or AA 478-910 of SEQ ID NO: 2 and a functional fragment of the PIN domain comprising at least 80% identity to a sequence AA 1-217 of SEQ ID NO: 1 or AA 1-241 of SEQ ID NO: 2, wherein DIS3 or the DIS3 fragment comprises a mutation in the RNB domain, wherein the DIS3 or the DIS3 fragment is an isolated protein or is in a cell line or yeast strain, wherein the mutation is found as occurring in hDIS3 in cancer cells, b) contacting the model system obtained in a) with a tested agent wherein the tested agent may inhibit DIS3 PIN domain endonuclease activity, and c) measuring the activity of the PIN domain in the presence and absence of the tested agent, wherein this measuring is by assessing DIS3 PIN endoribonuclease activity, cellular growth or cell viability or examining exosome substrates in the presence and absence of the tested agent.