Imagine building a microscopic structure the way you’d assemble modular furniture—using a handful of standardized parts that can be taken apart and rebuilt into something entirely new. Researchers at UCLA and the University of Rome Tor Vergata have made this vision a reality, developing synthetic genes that function like biological ones, unlocking new ways to create and deconstruct biomolecular materials.

The research, published in Nature Communications, is led by Elisa Franco, a professor at UCLA Samueli School of Engineering, and features postdoctoral scholar Daniela Sorrentino as the study's first author. The team’s groundbreaking approach mimics nature’s use of gene cascades for timed cellular development but with a synthetic twist.

Modular Biology: Nature’s Playbook Reimagined

In nature, complex life forms develop through precisely timed gene cascades that dictate when and where specific cellular structures emerge. A vivid example is the process in fruit flies, where an orchestrated series of genetic activations shapes the insect’s body segments in perfect order. This elegant mechanism inspired Franco and her team to replicate similar functionality in the lab.

“We had the idea of recreating in the lab similar gene cascades that, depending on the timing of gene activation, could induce the formation, or the disassembly, of synthetic materials,” said Francesco Ricci, a co-author and professor of chemical science at the University of Rome Tor Vergata.

Building Blocks of Innovation

The researchers worked with DNA tiles—small, synthetic DNA strands capable of self-assembling into complex structures. By programming synthetic genes to produce RNA triggers at specific times, the team created a solution teeming with DNA tiles that formed into micron-scale tubes only when an RNA signal was present. A different RNA trigger could command these structures to dissolve, showcasing the flexibility of the method.

“Our work suggests a way toward scaling up the complexity of biomolecular materials by taking advantage of the timing of molecular instructions for self-assembly rather than by increasing the number of molecules carrying such instructions,” Franco explained. The research highlights how a finite set of building blocks can be rewired and reused to create different materials, offering a new level of sophistication in synthetic biology.

Sorrentino added, “By coordinating these signals, we can assign different functions to the same components, creating materials that spontaneously evolve from the same parts. This opens up exciting advances in synthetic biology and paves the way for new applications in medicine and biotechnology.”

The implications of this work extend far beyond simple DNA structures. The method can be applied to other materials and systems reliant on biochemical signaling, presenting the potential for synthetic systems that adapt, reconfigure, or disassemble based on timed genetic instructions.