Method of efficiently establishing induced pluripotent stem...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/113 (2010.01) C12N 5/071 (2010.01) C12N 5/10 (2006.01) C12N 15/00 (2006.01) A61K 31/7088 (2006.01)

Patent

CA 2695590

The present invention provides a method of improving the efficiency of establishment of induced pluripotent stem (iPS) cells, comprising inhibiting the p53 function in the step of somatic cell nuclear reprogramming. The inhibition of p53 function is achieved by bringing a substance selected from the group consisting of (1) chemical inhibitors of p53, (2) dominant negative mutants of p53 and nucleic acids that encode the same, (3) siRNAs and shRNAs against p53 and DNAs that encode the same, and (4) p53 pathway inhibitors, into contact with a somatic cell, and the like. The present invention also provides an agent for improving the efficiency of establishment of iPS cells, the agent comprising an inhibitor of p53 function, particularly (1) chemical inhibitors of p53, (2) dominant negative mutants of p53 and nucleic acids that encode the same, (3) siRNAs and shRNAs against p53 and DNAs that encode the same, and (4) p53 pathway inhibitors. The present invention further provides a method of producing an iPS cell, comprising bringing a nuclear reprogramming substance and an inhibitor of p53 function into contact with a somatic cell.

La présente invention concerne un procédé d'amélioration de l'efficacité d'établissement de cellules souches pluripotentes induites (iPS), comprenant l'étape consistant à inhiber la fonction p53 dans l'étape de reprogrammation nucléaire des cellules somatiques. L'inhibition de la fonction p53 est obtenue en amenant une substance choisie dans le groupe comprenant (1) des inhibiteurs chimiques du p53, (2) des mutants négatifs dominants du p53 et des acides nucléiques qui codent pour ceux-ci, (3) des ARNsi et des ARNsh contre le p53 et des ADN qui codent pour ceux-ci, et (4) des inhibiteurs de la voie du p53, en contact avec une cellule somatique, et équivalents. La présente invention concerne également un agent pour améliorer l'efficacité d'établissement de cellules iPS, l'agent comprenant un inhibiteur de la fonction p53, en particulier (1) des inhibiteurs chimiques du p53, (2) des mutants négatifs dominants du p53 et des acides nucléiques qui codent pour ceux-ci, (3) des ARNsi et des ARNsh contre le p53 et des ADN qui codent pour ceux-ci, et (4) des inhibiteurs de la voie du p53. La présente invention concerne en outre un procédé de production d'une cellule iPS, comprenant l'étape consistant à amener en contact une substance de reprogrammation nucléaire et un inhibiteur de la fonction p53 avec une cellule somatique.

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