Methods and kits for drug screening and toxicity testing using promoter-reporter cells derived from embryonic stem cells
First Claim
1. A method of drug testing, comprising:
- a) combining the drug with a cell population differentiated from human embryonic stem (hES) cells, comprising cells that have been genetically altered so that a promoter that responds to a metabolic or toxicologic change in the cell controls expression of a reporter gene; and
then b) determining whether there is a change in expression of the reporter gene.
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Abstract
This invention provides a system for rapid determination of pharmacologic effects on target tissue types in cell populations cultured in vitro. The cells contain a promoter-reporter construct that reflects a toxicologic or metabolic change caused by the agent being screened. The promoter is taken from a gene known to be up- or down-regulated according to the metabolic state of the cell, and linked to a reporter gene that provides an external signal for monitoring promoter activity. The promoter-reporter cells may be produced by placing these genetic alterations into a line of human embryonic stem cells, bulking up the cells to any extent desired, and then differentiating the cells into the desired tissue type. This disclosure explains some of the powerful features of the promoter-reporter cells of this invention, and shows various ways the skilled reader can use the invention for pharmaceutical development and testing, or to monitor graft survival.
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Citations
20 Claims
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1. A method of drug testing, comprising:
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a) combining the drug with a cell population differentiated from human embryonic stem (hES) cells, comprising cells that have been genetically altered so that a promoter that responds to a metabolic or toxicologic change in the cell controls expression of a reporter gene; and
thenb) determining whether there is a change in expression of the reporter gene. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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- 17. Isolated tissue prepared for transplantation and adapted for monitoring after engraftment into a subject, containing cells differentiated from hES cells that have been genetically altered so that a promoter that responds to a metabolic or toxicologic change in the cell controls expression of a reporter gene.
Specification