Efficient induction of pluripotent stem cells using small molecule compounds: RepSox
Chemical induction of iPS cells
Reprogramming somatic cells to a pluripotent state could generate a rich supply of patient-specific stem cells for regenerative medicine. Recent work has demonstrated that exogenous expression of four transcription factors- Sox-2, Oct-4, Klf-4, and c-Myc, or Sox-2, Oct-4, Nanog, and Lin-28, can directly reprogram somatic cells to a pluripotent stem cell state. However, current viral transduction methods used to deliver these reprogramming factors increase the risk of cancer because the viral transgenes may spontaneously re-activate. Therefore, the resulting induced pluripotent stem (iPS) cells are unsuitable for regenerative medicine and suboptimal for disease modeling. Future clinical applications will require the elimination of the viral transgenes from iPS cells.
Innovations and Advantages
Using a phenotypic chemical screen, scientists of Harvard University have identified RepSox, a small molecule inhibitor of TGF-beta signaling, can replace one of the four reprogramming factors Sox-2. RepSox was successfully used in the direct reprogramming of mouse fibroblasts through induction of Nanog transcription. Human applications of this technology are being investigated.
Intellectual Property Status: Patent pending.
Justin K. Ichida, Joel Blanchard, Kelvin Lam, Esther Y. Son, Julia E. Chung, Dieter Egli, Kyle M. Loh, Ava C. Carter, Francesco P. Di Giorgio, Kathryn Koszka, Danwei Huangfu, Hidenori Akutsu, David R. Liu, Lee L. Rubin, Kevin Eggan. 2009. A Small-Molecule Inhibitor of TGF-beta Signaling Replaces Sox2 in Reprogramming by Inducing Nanog. Cell Stem Cell 5(5), 491-503.
Eggan, Kevin Carl
Ichida, Justin K.
Rubin, Lee L.
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Vivian Berlin, Director of Business Development
Reference Harvard Case #3330