RNA CAD tool for synthetic biology may facilitate RNA nanotechnology

New computer assisted design (CAD) tools for engineering RNA components have been developed for the growing field of synthetic biology. The knowledge of RNA folding and RNA catalytic and binding functions incorporated into these CAD tools may also prove useful for RNA nanotechnology. A hat tip to Science Daily for reprinting this news release from the Lawrence Berkeley National Laboratory (Berkeley Lab) “CAD for RNA“:

The computer assisted design (CAD) tools that made it possible to fabricate integrated circuits with millions of transistors may soon be coming to the biological sciences. Researchers at the U.S. Department of Energy (DOE)’s Joint BioEnergy Institute (JBEI) have developed CAD-type models and simulations for RNA molecules that make it possible to engineer biological components or “RNA devices” for controlling genetic expression in microbes. This holds enormous potential for microbial-based sustainable production of advanced biofuels, biodegradable plastics, therapeutic drugs and a host of other goods now derived from petrochemicals.

“Because biological systems exhibit functional complexity at multiple scales, a big question has been whether effective design tools can be created to increase the sizes and complexities of the microbial systems we engineer to meet specific needs,” says Jay Keasling, director of JBEI and a world authority on synthetic biology and metabolic engineering. “Our work establishes a foundation for developing CAD platforms to engineer complex RNA-based control systems that can process cellular information and program the expression of very large numbers of genes. Perhaps even more importantly, we have provided a framework for studying RNA functions and demonstrated the potential of using biochemical and biophysical modeling to develop rigorous design-driven engineering strategies for biology.” …

The ressearch was published in Science [abstract]. To test their CAD tools, the researchers engineered 28 molecular devices to regulate metabolic pathways in bacteria via RNA-controlled gene expression, and verified that expected levels of expression were obtained. From the abstract, “… More broadly, we provide a framework for studying RNA functions and illustrate the potential for the use of biochemical and biophysical modeling to develop biological design methods.”

The news release continues:

… As with other engineering disciplines, CAD tools for simulating and designing global functions based upon local component behaviors are essential for constructing complex biological devices and systems. However, until this work, CAD-type models and simulation tools for biology have been very limited.

Identifying the relevant design parameters and defining the domains over which expected component behaviors are exerted have been key steps in the development of CAD tools for other engineering disciplines,” says Carothers, a bioengineer and lead author of the Science paper who is a member of Keasling’s research groups with both JBEI and the California Institute for Quantitative Biosciences. “We’ve applied generalizable engineering strategies for managing functional complexity to develop CAD-type simulation and modeling tools for designing RNA-based genetic control systems. Ultimately we’d like to develop CAD platforms for synthetic biology that rival the tools found in more established engineering disciplines, and we see this work as an important technical and conceptual step in that direction.” …

RNA nanotechnology has a unique set of advantages as a pathway technology toward atomically precise productive nanosystems that reflect its central role in biological systems. Unlike the simple Watson-Crick base-pair molecular recognition code that underlies DNA nanotechnology, the more complex rules of base-pairing involved in RNA folding allow RNA to fold into compact complex three-dimensional shapes. These shapes are somewhat reminiscent of the complex folds of protein structures, yet the folding rules are considerably simpler than those of proteins. These RNA CAD tools may be an important step toward powerful design tools for folded polymer paths toward molecular machine systems.

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