Leonard and his team have developed a technology for
engineering human cell-based 'devices' that monitor and modify human physiology.
This technology is a protein biosensor that sits on the surface of a cell, can
be programmed to sense …more
Engineering cell-based, biological devices that
monitor and modify human physiology is a promising frontier in clinical
synthetic biology. However, no existing technology enabled bioengineers to build
such devices that sense a patient's physiological state and respond in a
"The project addressed a key gap in the synthetic
biology toolbox," says Joshua Leonard, assistant professor of chemical and
biological engineering in Northwestern's McCormick School of Engineering and
Applied Science. "There was no way to engineer cells in a manner that allowed
them to sense key pieces of information about their environment, which could
indicate whether the engineered cell is in healthy tissue or sitting next to a
Funded by the National Academies Keck Futures
Initiative and the Defense Advanced Research Projects Agency, the research is
available to read online in the journal ACS Synthetic Biology.
Leonard's team worked for nearly four years to close
this gap. The end result is a protein biosensor that sits on the surface of a
cell and can be programmed to sense specific external factors. For example, the
engineered cell could detect big, soluble protein molecules that indicate that
it's next to a tumor. When the biosensor detects such a factor, it sends a
signal into the engineered cell's nucleus to activate a gene expression program,
such as the production of tumor-killing proteins or chemicals. Since this toxic
program would be activated only near tumor cells, such an approach could
minimize side effects as well as improve therapeutic benefits.
Called a Modular Extracellular Sensor Architecture
(MESA), the biosensor platform is completely self-contained so that several
different biosensors can be present in a single cell without interfering with
one another, allowing bioengineers to build increasingly sophisticated
functional programs. The platform is also highly modular, enabling the
biosensors to be customized to recognize factors of relevance to various
"By linking the output of these biosensors to
genetic programs, one can build in a certain logical command, such as 'turn the
output gene on when you sense this factor but not that factor,'" Leonard
explains. "In that way, you could program a cell-based therapy to specify which
cells it should kill."
Leonard says doctors could potentially collect
immune cells from a patient's body, engineer the cells using MESA, and put them
back into the patient. From there, the cells would do the work of detecting
cancer or the disease they are designed to identify.
This is the first completely ground-up engineering
of a receptor, and now that the core technology has been established, Leonard's
team is moving forward to program
cells to recognize specific tumor-associated factors. They are also looking
toward applications beyond advanced cell-based therapies.
"This seems to be what always happens in
synthetic biology," he says. "When you start building something, you first
learn a lot about the system that you are trying to modify. In the end, you come
up with not only useful applications but tools that facilitate basic science."
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