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Researchers have created synthetic genes that mimic the functions of genes found in living cells. These artificial genes can construct intracellular structures using a step-by-step process that assembles self-forming structures incrementally. This groundbreaking finding could lead to the development of intricate biomolecular materials from simple, programmable building blocks, such as nanoscale tubes crafted from DNA tiles. Moreover, these same components can be directed to disassemble, allowing for the creation of different materials.
A team of researchers from UCLA’s Samueli School of Engineering and the University of Rome Tor Vergata in Italy have created synthetic genes that operate like natural genes within living cells.
These synthetic genes can create intracellular structures through a cascading process that assembles self-forming architectures gradually. This method is akin to constructing furniture from modular parts, similar to items sold at IKEA. With the same components, one can create various designs and easily take them apart to reconstruct new formations. This discovery paves the way for utilizing versatile building blocks that can be programmed to produce sophisticated biomolecular materials, including nanoscale tubes formed from DNA tiles. These components can also be programmed to disassemble, allowing for different material configurations.
The study, recently published in Nature Communications, was led by Elisa Franco, a professor in mechanical and aerospace engineering as well as bioengineering at UCLA Samueli. Daniela Sorrentino, a postdoctoral researcher in Franco’s Dynamic Nucleic Acid Systems lab, is the principal author of the study.
“Our findings indicate a method to increase the complexity of biomolecular materials by leveraging the timing of molecular instructions necessary for self-assembly, reducing the need to use a larger number of molecules that carry such instructions,” Franco explained. “This reveals an exciting opportunity to create diverse materials that can automatically ‘evolve’ from the same limited set of parts by simply adjusting the timing of the assembly instructions.”
Complex organisms arise from a single cell through a series of division and differentiation events. These procedures involve numerous biomolecules that are coordinated by gene cascades, which direct when and where specific genes are activated. When a cellular signal is detected, it sets off a sequence of genes that assemble in a predetermined order, resulting in a particular biological response. A prime example in biology is the gene cascade that governs the development of body segments in fruit flies. In this case, genes are intricately timed to facilitate the emergence of specific body segments accurately.
“We aimed to replicate similar gene cascades in the lab that could trigger the formation or disassembly of synthetic materials based on the timing of gene activation,” remarked co-author Francesco Ricci, a professor of chemical science at the University of Rome Tor Vergata.
For this research, the team utilized DNA tiles made up of a few synthetic DNA strands. They created a solution containing millions of these tiles, which interacted with one another to produce tubular structures at the micron scale. The formation of these structures is contingent upon the presence of a specific RNA molecule that initiates the process. A different RNA trigger can also stimulate the disassembly of the same structures.
Subsequently, they programmed various synthetic genes to produce the RNA triggers at precise intervals, allowing for accurate timing of both the formation and breakdown of the DNA structures.
By linking these genes, they established a synthetic genetic cascade, akin to that of a fruit fly, capable of controlling not just when a particular type of DNA structure is formed or broken down, but also its specific compositional attributes at designated times.
“Our method is not confined to DNA structures; it can be applied to various materials and systems that depend on the timing of biochemical signals,” Sorrentino noted. “By coordinating these signals, we can assign multiple functions to identical components, resulting in materials that can autonomously evolve from the same building blocks. This presents exciting prospects in synthetic biology and paves the way for innovative applications in medicine and biotechnology.”
This research received funding 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, as well as Italy’s National Recovery and Resilience Plan financed through the European Union’s NextGenerationEU stimulus package. Sorrentino holds a fellowship supported by the Italian Association for Cancer Research.
Additionally, Simona Ranallo, a researcher from the University of Rome Tor Vergata, contributed as a co-author of this study.
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