University of Heidelberg


10.09.18 10:28 Age: 3 yrs

Researchers at BioQuant use synthetic viral vectors to reprogram cells in vivo into pluripotency


Publication in Nature Communications

The ability to reprogram somatic mammalian cells into induced pluripotent stem cells (iPSC) by over-expressing a cocktail of transcription factors - typically Oct-3/4 (O), Klf4 (K), Sox2 (S) and c-Myc (M) - holds tremendous potential for basic research and regenerative medicine.

In a study recently published in Nature Communications, the laboratory of Dirk Grimm demonstrates, for the first time, the feasibility to deliver and express the OKSM cocktail in adult mice, using recombinant Adeno-associated viruses (AAV) as potent vehicles. To this end, the group teamed up with the laboratory of Manuel Serrano at the Spanish National Cancer Research Centre (CNIO) in Madrid, who had previously reported efficient in vivo reprogramming in mice that inherently over-express the OKSM factors.

Together, the two teams now show that ectopic OKSM expression with AAV vectors can likewise trigger in vivo dedifferentiation of somatic cells in an adult organism, evidenced by formation of teratomas (i.e., benign tissue derived from iPSC) and the detection of circulating iPSC in the blood of treated animals.

To further improve the safety and specificity of this exciting novel technology, and hence its clinical applicability, the Grimm laboratory is currently designing and testing second-generation, physically or pharmacologically inducible AAV/OKSM vectors in close collaboration with another BioQuant team (Dominik Niopek) and a group at the German Cancer Research Center Heidelberg (DKFZ, Ana Martin-Villalba).





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