Selective antibody targeting of undifferentiated stem cells

Abstract

This invention provides a system for producing differentiated cells from a stem cell population for use wherever a relatively homogenous cell population is desirable. The cells contain an effector gene under control of a transcriptional control element (such as the TERT promoter) that causes the gene to be expressed in relatively undifferentiated cells in the population. Expression of the effector gene results in expression of a cell-surface antigen that can be used to deplete the undifferentiated cells. Model effector sequences encode glycosyl transferases that synthesize carbohydrate xenoantigen or alloantigen, which can be used for immunoseparation or as a target for complement-mediated lysis. The differentiated cell populations produced are suitable for use in tissue regeneration and non-therapeutic applications such as drug screening.

1 . A stem cell genetically altered to express a carbohydrate antigen not normally expressed by the cell.  
     
     
         2 . The stem cell of  claim 1 , wherein expression of the carbohydrate antigen is controlled by a transcriptional control element that preferentially causes expression in undifferentiated cells.  
     
     
         3 . The stem cell of  claim 2 , wherein the transcriptional control element is an OCT-4 promoter or a promoter of telomerase reverse transcriptase (TERT).  
     
     
         4 . The stem cell of  claim 1 , genetically altered with a glycosyltransferase.  
     
     
         5 . The stem cell of  claim 4 , wherein the glycosyltransferase is an α(1,3)galactosyltransferase.  
     
     
         6 . The stem cell of  claim 4 , wherein the glycosyltransferase is an ABO blood group transferase.  
     
     
         7 . The stem cell of  claim 1 , which is a human embryonic stem (hES) cell.