Scientists from the University of Rome Tor Vergata in Italy and the UCLA Samueli School of Engineering have created artificial genes that work similarly to those found in living cells. Through a cascading sequence that constructs self-assembling structures piece by piece, the artificial genes are able to construct intracellular structures. The method is comparable to using modular units, such those sold at IKEA, to construct furniture. It is simple to disassemble the kit and reassemble the components for another project, and the same parts can be used to produce a wide variety of objects. The finding provides a way to create sophisticated biomolecular materials, including nanoscale tubes made from DNA tiles, using a set of basic building blocks that can be controlled.
Their findings were published in the journal Nature Communications.
Elisa FrancoOur 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,
This points to the exciting possibility of generating distinct materials that can spontaneously ‘develop’ from the same finite set of parts by simply rewiring the elements that control the temporal order of assembly.
From a single cell, complex organisms are created through a series of division and differentiation processes. Numerous biomolecules are involved in these processes, which are regulated by gene cascades that control the location and timing of gene activation. A specific biological response results from the assembly of a set of genes in a certain order in response to a chemical signal. The gene cascade that regulates the development of body segments in fruit flies is a well-known example in biology. Genes are precisely positioned to initiate the development of particular body parts in the right sequence during this process.
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.
Franceso Ricci
The researchers utilized a few synthetic DNA strands to create the building blocks of DNA tiles for their investigation. Millions of these tiles were then combined to produce a solution, and as they interacted, micron-scale tubular structures were formed. Only when a particular RNA molecule is present does the structure start to form. The identical structures can alternatively be made to disassemble by a separate RNA trigger molecule.
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Then, in order to precisely time the construction and disintegration of the DNA structures, they coded several synthetic genes that generate the RNA triggers at particular moments.
By joining these genes, they produced a synthetic genetic cascade that functions similarly to a fruit fly’s and can regulate not only the formation or dissolution of a certain type of DNA structure but also its particular compositional characteristics at a given moment.
Our approach is not limited to DNA structures, it can be extended to other materials and systems that rely on the timing of biochemical signals,
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.
Sorrentino
The European Research Council, the Italian Association for Cancer Research, the Italian Ministry of University and Research, the U.S. Department of Energy’s Office of Science, the U.S. National Science Foundation, and Italy’s National Recovery and Resilience Plan, which is funded by the European Union’s NextGenerationEU stimulus package all provided support for the study. Sorrentino is the recipient of an Italian Association for Cancer Research fellowship.
Source: UCLA – Samueli School of Engineering
Journal Reference: Sorrentino, Daniela, et al. “Developmental Assembly of Multi-component Polymer Systems through Interconnected Synthetic Gene Networks in Vitro.” Nature Communications, vol. 15, no. 1, 2024, pp. 1-13, DOI: https://doi.org/10.1038/s41467-024-52986-z.
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