Using a protein from the human retina, researchers in Switzerland have developed a method to control the expression of target genes with light. The scientists say the technology could be employed in the near term to boost the production of biological drugs, such as those for cancer, by enabling precise control over protein production. In the long term, cells engineered to carry the light-sensitive switch could be implanted into patients to produce a missing hormone, such as insulin, on demand.
Martin Fussenegger and collaborators at the Swiss Federal Institute for Technology engineered cells to carry the gene for a light-sensitive protein from the human retina, called melanopsin, which triggers a surge in calcium inside the cell when exposed to light. That calcium surge activates a second component, a protein that can be linked to any gene of interest. Shining light on the cells triggers the calcium, which activates the protein, thereby turning on the target gene. According to experiments in cultured cells, the timing and intensity of light controls both the amount and timing of the gene produced.
Researchers demonstrated the technology by implanting light-controlled cells into diabetic mice and using light to manipulate the animals’ insulin levels. When the cells were implanted just beneath the skin, exposure to blue light triggered insulin production. In a second experiment, researchers encapsulated the cells in a porous material and implanted them more deeply into the body, along with a fiber-optic cable to deliver light when needed. Both methods were able to control the animals’ blood sugar. The research was published today in the journal Science.
The Swiss research is the latest effort to control increasingly complex biological functions with light. Most of the research has focused on brain cells, and activating and silencing them through light-sensitive channels—a rapidly growing field known as optogenetics. But a handful of researchers are fusing optogenetics techniques with synthetic biology, an offshoot of molecular biology that attempts to engineer cells to perform useful functions. “There’s a growing interest in using light as a trigger for different biological pathways,” says James Collins, a biological engineer at Boston University. Light, unlike most chemical triggers, can be delivered “in a very localized way,” says Collins.
In addition to insulin, the technology can potentially deliver other types of therapeutic proteins, such as human growth hormone, Fusseneger says. Currently, these proteins are produced by engineered cells growing in a bioreactor, he says, and then delivered by injection or another method. “But now you could produce it in the patient and get the dosing right not by injection but by applying light.”
In fact, Fussenegger says, one of the near-term applications for the research is in biopharmaceutical manufacturing, the production of therapeutic proteins in bioreactors. Many such proteins are toxic to the cells in which they are grown, impeding production. But if protein production could be precisely controlled with light, researchers could grow the cells first and then activate production of the protein, tuning production on and off as needed to maintain the health of the cells.