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Scientists from UCLA’s Samueli School of Engineering and the University of Rome Tor Vergata have successfully engineered synthetic genes that mimic the functions of natural genes found in living organisms.
The constructed artificial genes are capable of forming intracellular structures through a well-defined sequence, leading to the emergence of self-assembling frameworks. This method draws a parallel to assembling modular furniture, akin to assembling products from IKEA, where the same components can be utilized in various configurations and can be easily reassembled into different structures. This innovative approach provides a promising avenue for developing complex biomolecular materials, including nanoscale tubes made from DNA tiles. The same basic components can also be programmed for disassembly, enabling the creation of distinct materials.
The findings were recently shared in Nature Communications, with lead researcher Elisa Franco, who is a professor in both mechanical and aerospace engineering and bioengineering at UCLA Samueli. Daniela Sorrentino, a postdoctoral researcher in Franco’s Dynamic Nucleic Acid Systems lab, took the lead as the first author of the study.
“Our research indicates a method for enhancing the complexity of biomolecular materials by utilizing the timing of molecular instructions for self-assembly, instead of simply increasing the quantity of molecules that carry these instructions,” Franco explained. “This reveals the thrilling potential of fabricating unique materials that can naturally ‘evolve’ from a limited set of components by merely rearranging the elements governing the order of assembly over time.”
The study draws inspiration from how complex organisms progress from a singular cell through successive division and differentiation processes. These biological events are facilitated by various biomolecules that are coordinated by gene cascades dictating when and where gene activation occurs. An illustrative example of this can be found in the fruit fly, where a specific gene cascade precisely regulates the formation of body segments in a timely manner.
“We aimed to replicate such gene cascades in the lab, where variations in gene activation timing could trigger either the formation or breakdown of synthetic materials,” noted co-author Francesco Ricci, a chemical science professor at the University of Rome Tor Vergata.
The researchers utilized building blocks made of DNA tiles, crafted from a few synthetic DNA strands. They synthesized a solution containing millions of these tiles, which interacted to create micron-scale tubular structures. Notably, these structures were only formed in the presence of a specific RNA molecule that acts as a trigger, while a different RNA trigger can promote the dissolution of these structures.
They went on to program synthetic genes that produced RNA triggers at calculated intervals, allowing for precise timing in the assembly and disassembly of the DNA structures.
By linking these genes, the team established a synthetic genetic cascade akin to that in fruit flies, which governs not only the timing of DNA structure formation and breakdown but also enables control over their specific compositional characteristics at designated moments.
“Our methodology is versatile and not confined to DNA structures; it can be applied to other materials and systems that depend upon the timing of biochemical signals,” Sorrentino remarked. “By synchronizing these signals, we can endow various functions to the same components, facilitating the spontaneous evolution of materials from identical building blocks. This advancement heralds significant progress in synthetic biology and paves the way for emerging applications in medicine and biotechnology.”
The research received support from the U.S. Department of Energy’s Office of Science, the U.S. National Science Foundation, the European Research Council, the Italian Association for Cancer Research, the Italian Ministry of University and Research, and Italy’s National Recovery and Resilience Plan, funded by the European Union’s NextGenerationEU stimulus package. Additionally, Sorrentino is supported by a fellowship from the Italian Association for Cancer Research.
Simona Ranallo, another researcher from the University of Rome Tor Vergata, is also acknowledged as a co-author of the study.
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