Methods and platforms for drug discovery

Abstract

The present invention involves methods for identifying an agent that corrects a phenotype associated with a health condition or a predisposition for a health condition. The invention also involves methods for identifying a diagnostic cellular phenotype, determining the risk of a health condition in a subject, methods for reducing the risk of drug toxicity in a human subject, and methods for identifying a candidate gene that contributes to a human disease. The invention also discloses human induced pluripotent stem cell lines.

1 . A method for identifying an agent that corrects a phenotype associated with a health condition or a predisposition for the health condition, comprising:
 (i) contacting a first population of cells from a human induced pluripotent stem cell line, or cells differentiated from the human induced pluripotent stem cell line, with a candidate agent;   (ii) contacting a second population of cells from the human induced pluripotent stem cell line, or cells differentiated from the human induced pluripotent stem cell line, with a negative control agent;   (iii) assaying the phenotype in the first population and second population after the contacting steps; and   (iv) identifying the candidate agent as correcting the phenotype if the assayed phenotype of the first population after the contacting step is closer to a normal phenotype than the phenotype of the second population after the contacting step;   wherein the cells in the first and second populations of human induced pluripotent stem cells:
 (a) comprise at least one endogenous allele associated with the health condition or the predisposition for the health condition; or 
 (b) are generated from a subject suffering from the health condition or the predisposition for the health condition. 
   
     
     
         2 - 46 . (canceled) 
     
     
         47 . A method for evaluating a physiological function of a compound comprising treating cells obtained by inducing differentiation of an induced pluripotent stem (iPS) cell with the compound, wherein the iPS cell is obtained by nuclear reprogramming of a somatic cell, which comprises contacting a nuclear reprogramming factor with the somatic cell to obtain an induced pluripotent stem cell. 
     
     
         48 . A method for evaluating the toxicity of a compound comprising treating cells obtained by inducing differentiation of an induced pluripotent stem (iPS) cell with the compound, wherein the iPS cell is obtained by nuclear reprogramming of a somatic cell, which comprises contacting a nuclear reprogramming factor with the somatic cell to obtain an induced pluripotent stem cell. 
     
     
         49 . A method for evaluating the effect of a compound on a cellular phenotype comprising treating cells obtained by inducing differentiation of an induced pluripotent stem (iPS) cell with the compound, wherein the iPS cell is obtained by inducing pluripotency of a somatic cell, which comprises contacting an induction factor with the somatic cell to obtain an induced pluripotent stem cell. 
     
     
         50 . A method for evaluating the toxicity of a compound comprising treating cells obtained by inducing differentiation of an induced pluripotent stem (iPS) cell with the compound, wherein the iPS cell is obtained by inducing pluripotency of a somatic cell, which comprises contacting an induction factor with the somatic cell to obtain an induced pluripotent stem cell.