Interdisciplinary Initiatives Program Round 5 – 2010
Marius Wernig, Pathology
Tobias Meyer, Chemical & Systems Biology
We have shown that mouse and human fibroblasts can be directly converted into neuronal cells following retroviral expression of 3 or 4 neuronal transcription factors. These induced neuronal (iN) cells showed all molecular and functional properties of neurons. This finding is exciting because lost neurons in e.g. neurodegenerative diseases could be replaced with the patients’ own neuronal cells. In addition patient-derived neuronal cells could be tested for the presence of disease properties. This could be used to try to capture and model disease processes that occur in the patients’ brains in iN cells. However, before iN cells could be used clinically the transcription factors will need to be delivered without viruses that could potentially cause cancer. We therefore proposed here to develop a method to generate iN cells without the risk of introducing mutations by delivering the the direct precursors of the factors, the so-called mRNAs. In addition to the increased safety of these cells, we have good reason to believe this approach will be much more efficient to generate the desired cells. This improved method could then be also used to study disease processes in iN cells derived from affected patients suffering from various brain diseases. We capitalize of the collaboration between the Wernig group – experts in generating iN cells and the Meyer group – experts in RNA delivery.