Stanford bioengineers develop tool for reprogramming genetic code
By selectively manipulating how DNA issues biological commands, Stanford bioengineers have developed a tool that could prove useful in future gene therapies.
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Stanford bioengineers have developed a new tool that allows them to preferentially activate or deactivate genes in living cells.
Biology relies upon the precise activation of specific genes to work properly.
Now, bioengineers at Stanford and other universities have developed a sort of programmable genetic code that allows them to preferentially activate or deactivate genes in living cells. The work is published in the current issue ofCell, and could help usher in a new generation of gene therapies.
For the purposes of gene editing, scientists can control where the protein snips the genome, insert a new gene into the cut and patch it back together.
Inserting new genetic code, however, is just one way to influence how the genome is expressed.
It's this action that Lei Stanley Qi, an assistant professor of bioengineering and of chemical and systems biology at Stanford, and his colleagues aim to manipulate.
In a cell, the order or degree in which multiple genes are activated can produce different metabolic products.
"It's like driving a car. You control the wheel to control direction, and the engine to control the speed, and how you balance the two determines how the car moves," Qi said. "We can do the same thing in the cell by up- or downregulating genes, and produce different outcomes."
As a proof of principle, the scientists used the technique to take control of a yeast metabolic pathway, turning genes on and off in various orders to produce four different end products.They then tested it on two mammalian genes that are important in cell mobility, and were able to control the cell's direction and how fast it moved.
The ability to control genes is an attractive approach in designing genetic therapies for complex diseases that involve multiple genes, Qi said, and the new system may overcome several of the challenges of existing experimental therapies.
"Our technique allows us to directly control multiple specific genes and pathways in the genome without expressing new transgenes or uncontrolled behaviors, such as producing too much of a protein, or doing so in the wrong cells," Qi said. "We could eventually synthesize tens of thousands of RNA molecules to control the genome over a whole organism."
"That is what is so exciting about working at Stanford, because the School of Medicine's immunology group is just around the corner, and working with them will help us address how to do this without triggering an immune response," said Qi, who is a member of the interdisciplinaryStanford ChEM-H institute.
Stanford bioengineers develop tool for reprogramming genetic code
