Bioengineers at Rice University in Texas, US, have developed a ‘construction kit’ for creating synthetic sense-and-respond circuits in human cells, aiming to ‘revolutionise’ treatments for diseases such as cancer and autoimmune disorders.
The kit leverages phosphorylation, a cellular process integral to converting external signals into actions, such as movement or gene expression.
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Phosphorylation-based ‘signalling’ in multicellular organisms typically triggers a cascade effect, akin to falling dominoes. Prior attempts to leverage this for therapeutic applications in human cells were limited by the complexity of native signalling pathways, the university noted.
The approach of Rice’s team involves treating each stage of the cascade as an elementary unit, which can be assembled in new ways to forge new pathways linking cellular inputs to outputs. The challenge lay in establishing the rules for constructing, connecting, and fine-tuning these units, including the design of outputs both inside and outside the cell.
Their modular method demonstrated the ability to amplify weak signals into substantial outputs.
One of the key benefits of the new sense-and-respond circuit design claims to be the ‘rapidity’ of phosphorylation, taking mere seconds or minutes, allowing the synthetic circuits to potentially react to physiological changes.
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By GlobalDataThis is in stark contrast to earlier designs based on transcription processes, which could take hours to activate, the university noted.
The circuits were tested for sensitivity and responsiveness to external signals, such as inflammatory factors.
Demonstrating its practical application, the team engineered a circuit capable of detecting these factors, offering a method to manage ‘autoimmune flare-ups’ and mitigate toxicity in immunotherapy.
Rice Synthetic Biology Institute deputy director Caleb Bashor said: “This opens up the signalling circuit design space dramatically.
“It turns out, phosphorylation cycles are not just interconnected but interconnectable — this is something that we were not sure could be done with this level of sophistication before.”
