New technology enables predictive design of engineered human cells

A team from Northwestern University, US, have developed a design-driven process that can build complex genetic networks for cellular engineering. The new technology uses computational modelling to more efficiently identify useful genetic designs before building cells in the lab. 

“To engineer a cell, we first encode a desired biological function in a piece of DNA and that DNA programme is then delivered to a human cell to guide its execution of the desired function, such as activating a gene only in response to certain signals in the cell’s environment,” said lead researcher of the study, Joshua Leonard. 

“Model-guided design has been explored in cell types such as bacteria and yeast, but this approach is relatively new in mammalian cells,” said Joseph Muldoon, a recent doctoral student and the paper’s first author.

According to the researchers, like other synthetic biology technologies, a key feature of this approach is that it is intended to be readily adopted by other bioengineering groups.

The research team used a “toolkit” of genetic parts invented in Leonard’s lab and paired these parts with computational tools for simulating many potential genetic programmes before conducting experiments. They found that a wide variety of genetic programmes, each of which carries out a desired and useful function in a human cell, can be constructed so that each programme works as predicted. The designs also work first time.

“In my experience, nothing works like that in science; nothing works the first time. We usually spend a lot of time debugging and refining any new genetic design before it works as desired,” Leonard said. “If each design works as expected, we are no longer limited to building by trial and error. Instead, we can spend our time evaluating ideas that might be useful in order to hone in on the really great ideas.”

The genetic circuits developed and implemented in this study are also more complex than previous circuits. The researchers say this advance creates the opportunity to engineer cells to perform more sophisticated functions and make therapies safer and more effective.

“With this new capability, we have taken a big step in being able to truly engineer biology,” Leonard said.

The study was published in the journal Science Advances.