Artist’s interpretation of a “circuit cell”. Credit: Ella Marushchenko
For billions of years, cells have perfected their biological machinery for making proteins, sending signals, and responding to their environment. Now scientists are learning how to program some of those instructions themselves.
In a new study, researchers at the Hebrew University of Jerusalem engineered human cells to process several biological signals at once, perform simple logic, and choose a response. The work remains early and laboratory-based, but it points toward a future in which cell therapies might sense disease patterns and release treatment only under the right conditions.
The Cellular Circuit
Researchers led by Ph.D. student Keren Roas and Dr. Lior Nissim were initially preoccupied with solving a practical problem: how to make a human cell respond only when it sees the right combination of signals. A cancer-targeting cell, for example, should not attack after spotting one suspicious molecule. It should wait until several signs point to the same diseased tissue.
Older genetic circuits can do that, but often by chaining together one molecular switch after another. That makes the circuit harder to fit inside a cell and harder for the cell to run.
“Our new approach allows cells to carry out complex programs using far fewer calculations and genetic building blocks,” Dr. Nissim said in a statement. “This makes it possible to build much more advanced biological programs without losing functionality.”
The key tool was RNA trans-splicing. RNA is the working copy of genetic instructions. In trans-splicing, pieces from separate RNA molecules join together, making a new message the cell can read.
The researchers used that process to build AND gates, a basic logic operation in which a cell produces an output only when two inputs appear together. They then added synthetic microRNAs, small RNA molecules that can silence specific messages, and hybrid promoters, genetic switches that tune when genes turn on.
In lab-grown human cells, the circuits showed they could handle more than a simple on-off command. Some cells were made to respond differently depending on how many signals they detected. Others chose one response from several possible options.
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The researchers also built in a warning signal. When the cell received a confusing instruction—the biological equivalent of two commands arriving at once—it produced a separate alert instead of continuing as if nothing had happened.
To show how the system might one day be used in medicine, the team programmed cells to secrete IL-15, an immune protein that can help activate cancer-fighting immune cells.
What Comes Next
The experiments relied on engineered circuits delivered into cells under controlled lab conditions. The authors note several challenges ahead, including avoiding unwanted RNA interactions, limiting leaky genetic switches, and finding reliable ways to insert larger circuits into cell genomes.
A programmed immune cell inside a patient would need to read confusing biological signals, ignore false alarms, and act only in the right tissue. Cancer, autoimmune disease, and metabolic disorders rarely announce themselves with a single marker. They often involve combinations of signals.
That is where these circuits could be useful. A future therapeutic cell might check several disease clues before releasing a drug, activating an immune response, or shutting itself down.
For now, the advance gives synthetic biologists a smaller and more flexible set of parts for cellular decision-making. It brings living cells a step closer to behaving like tiny programmable devices.
The study was published in the journal Nature Communications.