Turning Cells into Programmable Medical Devices

Targeted delivery of drugs and proteins to modify metabolism and cell behavior may in the future be accomplished by engineered cells. Cells already do a great many useful things, so why reinvent the wheel when there is existing machinery that can be adapted to new purposes? This is a line of research with the potential to radically change the face of medicine and our own biology, leading to a future in which most of us have large numbers of enhanced and altered cells in every organ, monitoring and reacting to local conditions in order to help maintain the body against the processes of aging and disease far more effectively than our present evolved mechanisms can manage.

A synthetic biology team has created a new technology for modifying human cells to create programmable therapeutics that could travel the body and selectively target cancer and other sites of disease. "The project addressed a key gap in the synthetic biology toolbox. 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 tumor."

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 patients' needs. "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.' In that way, you could program a cell-based therapy to specify which cells it should kill."

Link: http://www.mccormick.northwestern.edu/news/articles/2014/04/building-smart-cell-based-therapies.html