Viruses Affect Cell Reprogramming

Viral vectors used to carry transcription factors that de-differentiate cells into a stem-cell-like state are themselves a key factor in efficient reprogramming.

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Wikimedia, Nissim Benvenisty.Triggering a pathway designed to sense viral infection can help boost generation of induced pluripotent stem cells (iPSCs), suggesting that the viruses used by many reprogramming methods influence the fate of the cell. The new research, published today (October 25) in Cell, suggests that targeting the pathway without using viruses could avoid the risk that the viruses’ genetic material will integrate into the genome and cause the cell to become cancerous—a common concern for iPSC therapies.

“This is something everyone else missed before,” said Gioacchino Natoli, an experimental oncologist at the European Institute of Oncology in Italy who was not involved in the study. An innate immune response to the viral vector is clearly needed for reprogramming, and “stimulating this leads to reprogrammed cells without exogenous DNA being integrated,” he added.

Six years ago, Shinya Yamanaka identified four key transcription factors, that, when transduced into cells using a viral vector, caused cells to de-differentiate into a stem-cell-like state, capable of generating a multiplicity of human tissues. He shared this year’s Nobel Prize in Medicine for the achievement, which has already made significant contributions to biomedical research. But there was a major hurdle on the path to clinical use: the strategy relies ...

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