The first protein-based nanocomputing agent that functions as a circuit has been created by researchers at Penn State University. This milestone brings us one step closer to developing the next generation of cell-based therapeutics to treat diseases such as diabetes and cancer.
Conventional synthetic biological approaches to cell-based therapies that destroy cancer cells or promote tissue regeneration after injury rely on the expression or suppression of proteins that produce desired effects within the cell. This approach is time consuming (protein expression and degradation) and can consume cellular energy in the process. A team of researchers at the Pennsylvania State University of Medicine and the Huck Institute for Life Sciences has taken a different approach.
“We are designing proteins that directly produce the desired effects,” said Nikolai Dohoryan, Professor G. Thomas Passananti and Associate Dean of Research at the School of Pharmacy. “Our protein-based devices or nanocomputing agents respond directly to stimuli (inputs) and produce desired actions (outputs).”
In a study published in scientific progress Today (May 26), Dokholyan and bioinformatics and genomics PhD student Jiaxing Chen discuss approaches to creating nanocomputing agents. They engineered target proteins by integrating two sensor domains, regions that respond to stimuli. In this case, the target protein responds to light and a drug called rapamycin by adjusting its orientation, or position in space.
To test the design, the team introduced engineered proteins into living cells in culture. By exposing cultured cells to stimuli, the researchers used a device that measured changes in cell orientation after the cells were exposed to stimulation of the sensor domain.
Previously, nanocomputing agents required two inputs to produce one output. Well, Chen says there are two possible outputs, and the output depends on the order in which the inputs are received. Cells adopt one angular cell orientation when rapamycin is detected first and then light, whereas cells adopt a different orientation angle when stimuli are received in the opposite order. Chen says this experimental proof-of-concept opens the door to the development of more complex nanocomputing agents.
“Theoretically, the more inputs we embed in a nanocomputing agent, the more possible outcomes we can get from different combinations,” Chen said. “Potential inputs include physical or chemical stimuli, and outputs include changes in cell behavior such as cell orientation, migration, altered gene expression, and immune cell cytotoxicity against cancer cells. there is a possibility.”
The team plans to further develop the nanocomputing agent and experiment with various applications of the technology. Dhorian, a researcher at the Pennsylvania State Cancer Institute and the Pennsylvania State Neuroscience Institute, said their concept could one day be the next generation of cells for a variety of diseases, including autoimmune diseases, viral infections, diabetes, nerve damage and cancer. said it could form the basis of a base therapy. .
Yashavantha Vishweshwaraiah, Richard Mailman, and Erdem Tabdanov of Pennsylvania State Medical College also contributed to the study. The authors declare no conflict of interest.
This study was funded by the National Institutes of Health (grant 1R35GM134864) and the Passan Foundation.
