To do so, they needed a technology that would allow them to silence genes without perturbing the cells in the process. Although RNA interference (RNAi) is a powerful way to turn off individual genes, most RNAi techniques rely on viruses as delivery vehicles. When scientists tried to perturb the T cells using these traditional techniques, cells either changed or died, limiting the effectiveness of these strategies.
"This was a real challenge," said Kuchroo. "Every time we tried to downregulate a gene with existing technologies, the cell would change. We didn't know if we were looking at the right thing. We needed a new technology something that could have a dramatic but precise effect."
A solution came from an unlikely source. Harvard professor and Broad associate member Hongkun Park and his lab in the departments of chemistry and chemical biology and of physics had been working on a computer-chip-like structure to interact with brain cells. Co-first authors Alex Shalek and Jellert Gaublomme along with other lab members had developed a bed of silicon nanowires miniscule needles designed to pierce cells.
"We learned that we could use these needles to deliver molecules into cells in a minimally invasive fashion," said Park. "And as Vijay and Aviv taught me, there are lots of things that this allows you to do that you could not do before. It's been an eye-opening experience."
Just as the thin needle of a syringe can be inserted into the skin and cause no more than a small pinching sensation, nanowires can be inserted into cells, causing minimal disruption. Using this new technology, the team teased apart the network, piece by piece, by deleting each of the key genes required in the development of Th17 cells.
With the help of co-first author Nir Yosef, a postdoc at the Broad and Brigham and Women's Hospital, the team found that Th17 cells are governed by two networks, seemingly at odds with each other: one
|Contact: Haley Bridger|
Broad Institute of MIT and Harvard