Massachusetts Institute of Technology

Khoury, Maroun

Drake, Adam C.

Leskov, Ilya B.

Pallasch, Christian

Hemann, Michael

Chen, Jianzhu

Michael Hemann

Douglas A Lauffenburger

Jianzhu Chen

Justin Pritchard

Hai Jiang

Maroun Khoury

Ilya B Leskov

Adam C Drake

Christian Pallasch

The invention is directed to a method of characterizing a mechanism of action of an agent (e.g., a chemotherapeutic agent, a genotoxic agent). The method comprises contacting a plurality of populations of cells with an agent to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein said gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the agent is determined, thereby obtaining an shRNA signature of the agent, so as to identify one or more genes that mediate a response to the agent, thereby characterizing the mechanism of action of the agent. The invention is also directed an article of manufacture for characterizing a mechanism of action of a chemotherapeutic or genotoxic agent.

RNAi-based method of drug screening and characterization

In one aspect, the invention is directed to a method of characterizing a mechanism of action of a combination of agents. The method comprises contacting a plurality of populations of cells with a combination of agents to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein the gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the combination of agents is determined, thereby obtaining an shRNA signature of the combination of agents so as to identify one or more genes that mediate a response to the combination of agents, thereby characterizing the mechanism of action of the combination of agents. In another aspect, the invention is directed to a method of determining whether a patient population treated with a first agent would benefit from a treatment using the first agent in combination with one or more additional agents. In yet another aspect, the invention is directed to method of determining whether a formulation of one or more agents maintains a mechanism of action of the one or more agents when unformulated.

RNAi-based method of screening and characterizing drug combinations

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Cambridge, MA, United States of America

Michael Hemann