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Researchers from Harvard’s Wyss Institute Develop Next-Generation Tools to Program Cells

Novel technology could convert cells into low-cost, efficient factories for producing biofuels, drugs, sugar, and other high value commodities

BOSTON — In what could be a significant step toward converting cells into tiny biological production facilities, researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a novel technology for controlling the behavior of a cell, in much the same way that an integrated circuit directs the behavior of a computer or a cell phone.

The research was led by the Wyss Institute’s Faisal Aldaye, Ph.D., a postdoctoral fellow, and Pamela Silver, Ph.D., a core faculty member. Their findings appear in today’s issue of Science.

Their new approach uses the nucleic acid, RNA, as a building block to construct scaffolding inside the cell to control its internal architecture and components. The scaffolding can be precisely programmed to trigger the metabolic reactions needed to produce a specific commodity, such as a drug, a biofuel, sugar or alcohol. Moreover, the rate at which that commodity is produced can also be controlled.

Using three different RNA scaffolds, researchers were able to produce three different levels of the biofuel hydrogen, representing a 4-fold, 11-fold, and 48-fold increase over production methods that do not involve scaffolding. This finding could help usher in a new age of low-cost, efficient hydrogen production. Long considered a promising alternative to fossil fuels, clean-burning hydrogen has been largely kept off the market because it is still expensive to produce in high volume.

"What’s so exciting about this new technology is that it has so much potential to address some critical real-world needs — from producing a clean fuel that will help the environment to producing a drug so economically that people around the world can afford it," says Silver.

The Wyss method represents a significant milestone in cell-programming technologies by enabling the production of nanodevices directly inside a living cell. While similar approaches using another nucleic acid — DNA — rather than RNA, as a building block are used now to produce nanocomponents for applications in electronics, optics and medicine, to date these methods have only been validated in a test tube — not in the natural environment of a living cell. That is partly because DNA represents a more challenging building material in this context, given our current biotechnological capabilities.

Using RNA instead, Aldaye and Silver were able to develop a technology for so precisely controlling the way it assembles itself inside a cell that they can now generate outcomes that would otherwise not occur naturally, such as the high level of hydrogen production.

"This is a paradigm shift in metabolic engineering," says Aldaye. "We are no longer limited by what exists in Nature. We are now able to redesign cells from the inside."

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