A team of researchers at Boston University has developed a new way to engineer mammalian cells that allows for programming them to behave in desired ways. In their paper published in the journal Nature Biotechnology, the team describes their technique and where they believe such technology is heading.
As scientists around the world look for new ways to prevent and treat diseases, new techniques are emerging, some of which involve programing human cells to behave in desired ways—such as killing cancer cells. In this new effort, the researchers have developed a new way to program mammalian cells using DNA recombinases.
To learn how to program cells researchers have worked with simple organisms such as bacteria, which has led to the use of proteins called transcription factors that regulate genes. Unfortunately, that technique has proven unsuitable for programming mammalian cells because it does not produce the same results consistently in all environments. To get around that problem, the researchers instead chose to work with DNA recombinases—enzymes that can be used to cut DNA in predesignated ways and put them back together in new and useful ways.
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| 16 types of Boolean values (Boolean operators) implemented using different locations of sites of two recombinases |
Cutting DNA and sewing it back together allows for programming cells because DNA controls which proteins a cell makes. By cutting and sewing in a certain way, the researchers were able to induce a human kidney cell to produce a fluorescent protein which caused the cell to light up under desired conditions. Inserting other snippets allowed for modifying recombinases that were activated only in the presence of a certain chemical. By cutting multiple DNA snippets, adding new ones and sewing them back together, the researchers found that they were able to create 113 unique circuits that demonstrated a 96.5 rate of success. In one instance, they created a bio-circuit that mimicked a Boolean lookup table—it had six inputs that allowed for executing 16 logical operations.
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| The work of four genes encoding different fluorescent proteins in 4 variants of system states (at the top - before the addition of doxycycline, at the bottom - at reaching its maximum concentration) |
The work by the team was a proof of concept, they're optimistic that their technique could be used to create new therapies such as bolstering the immune system by programming T cells—perhaps causing them to attack tumor cells. Another possibility is using the technique to program stem cells to grow into desired tissue.