Approach Summary Licensing status Publication and contact information Drug platforms Chemically mediated somatic cell reprogramming Cell-culture studies suggest that inhibitors of chromatin-modifying enzymes can increase the efficiency with which somatic cells are reprogrammed to pluripotent stem cells, providing a potential boon to the development of stem cell-based therapies. In mouse embryonic fibroblasts expressing four transcription factors (Oct4, Sox2, Klf4 and c-Myc) that are sufficient to induce pluripotency, small molecule inhibitors of DNA methyltransferase or histone deacetylase (HDAC) significantly increased reprogramming efficiency compared with that seen in dimethyl sulfoxide (DMSO)-treated controls (p<0.05). The HDAC inhibitor valproic acid (VPA) showed the strongest effect, with an increase of over 100-fold in programming efficiency compared with that seen in DMSO-treated controls (p<0.001). Next steps include assessing VPA's effects in human somatic cells and conducting a high throughput screen of small molecule libraries to identify other candidates for chemical-based cellular reprogramming. Patent pending for VPA effects on reprogramming; available for licensing through Harvard

Ectopic expression of defined sets of genetic factors can reprogram somatic cells to induced pluripotent stem (iPS) cells that closely resemble embryonic stem (ES) cells. The low efficiency with which iPS cells are derived hinders studies on the molecular mechanism of reprogramming, and integration of viral transgenes, in particular the oncogenes c-Myc and Klf4, may handicap this method for human therapeutic applications. Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two factors, Oct4 and Sox2, without the need for the oncogenes c-Myc or Klf4. The two factor-induced human iPS cells resemble human ES cells in pluripotency, global gene expression profiles and epigenetic states. These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical.