Duke researchers have developed a light-controlled system for controlling gene expression within living cells in a population.
This new technology, called LITEZ, offers researchers a method of mimicking the spatial patterns of gene expression used by nature during tissue development. It marks an advancement in the field of bioengineering that has important ramifications for cancer treatment, gene therapy, regenerative medicine and a vast range of other clinical and research applications.
“We already understand how cells themselves turn specific genes off and on,” said Huntington Willard, director of the Duke Institute of Genome Science and Policy. “The last step is being able to control gene expression ourselves at the level we want.”
LITEZ has the potential to solve this final problem. In addition to being relatively inexpensive and noninvasive, it also allows researchers to control genes of interest within a group of growing cells in a spatial, temporal, reversible and repeatable manner.
“Precise control of gene regulation is critical to all biological systems,” said Charles Gersbach, assistant professor of biomedical engineering, who worked on the project. “In the future, this system could be used for basic science research, biotechnology and medicine in applications such as gene therapy and regenerative medicine.”
To create this system, researchers extracted light-sensitive proteins from plants and combined these with engineered proteins that can be programmed to bind to particular parts of a gene. To test if these proteins could control genes in response to light stimulus, the researchers then delivered them into human cells that were subsequently cultured in the light and in the dark.
The scientists observed that they could control gene expression with this system based on several factors—the magnitude of the light, the duration of the light exposure and the spatial pattern in which the cells were exposed to the light.
Researchers hope that in the future, they will be able to use LITEZ to pattern the expression of genes that control tissue morphogenesis, said Lauren Polstein, a biomedical engineering graduate student who worked to develop the system.
“Successful patterning of certain genes may allow us to create tissue constructs in the lab that mimic those found naturally,” Polstein said. “The closer engineered tissues are to natural tissues with respect to patterns of gene expression and cell types, the more functional they will likely be when implanted into a patient.”
The system also holds important ramifications for the future of cancer research in that it provides a method of targeting events to specific tumor tissue in a manner that does not affect neighboring healthy cells.
“The ability to precisely control genes in time and space with light will allow us to recapitulate [natural] processes in the laboratory,” Gersbach said. “We hope these studies will ultimately lead to improvements in human health.”