Scientists Improve CRISPR Cas9 Tool for Microbes with Quantum Biology and AI, US

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Scientists at Oak Ridge National Laboratory (ORNL) have made significant advancements in the CRISPR Cas9 gene-editing tool used to modify microbes for renewable fuels and chemical production. By combining quantum biology, artificial intelligence (AI), and bioengineering, the researchers have improved the accuracy of the CRISPR Cas9 tool, particularly when applied to microbes with different chromosomal structures and sizes.

CRISPR Cas9 is a powerful bioengineering tool that modifies genetic code to enhance an organism’s performance or correct mutations. However, the existing models for designing CRISPR Cas9 tools were primarily developed for mammalian cells and other model species. When applied to microbes, these models showed weak and inconsistent efficiency due to differences in chromosomal structures. The team at ORNL sought to address this limitation by developing a more accurate and reliable method.

To enhance the modeling and design of guide RNAs—the RNA molecules that guide the Cas9 enzyme to the targeted site in the genome—the ORNL scientists looked into quantum biology. This interdisciplinary field examines the impact of electronic structure on the chemical properties of nucleotides, the building blocks of DNA and RNA. By considering quantum chemical properties, the scientists aimed to improve the effectiveness of the Cas9 enzyme-guide RNA complex binding with the microbe’s DNA.

The researchers employed an explainable AI model called iterative random forest, trained on a dataset of approximately 50,000 guide RNAs. This model not only took into account the quantum properties of nucleotides but also provided insights into the molecular mechanisms that underlie the efficiency of guide RNAs. By using the Summit supercomputer at ORNL, the team validated the AI model through CRISPR Cas9 cutting experiments on E. coli, using guides selected by the model.

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By incorporating quantum properties into guide RNA design, the improved CRISPR Cas9 tools have implications for a wide range of species, including humans. For instance, they can enhance the accuracy of targeted genetic modifications in drug development. Furthermore, these advancements contribute to functional genomics, enabling scientists to more effectively link genotype to phenotype, or genes to physical traits.

The ORNL synthetic biology team plans to collaborate with computational science colleagues to refine the microbial CRISPR Cas9 model further. By incorporating data from lab experiments and various microbial species, the researchers aim to continue improving the predictability and precision of CRISPR technology. Ultimately, these advancements have significant implications for various fields, including bioenergy production and the enhancement of bioenergy feedstock plants.

The research was supported by the Department of Energy’s Genomic Science Program and the Center for Bioenergy Innovation. By continually refining CRISPR Cas9 models and leveraging explainable AI modeling, scientists can better modify the DNA of organisms, avoiding costly errors and enabling more precise and efficient research in the future.

Frequently Asked Questions (FAQs) Related to the Above News

What is CRISPR Cas9?

CRISPR Cas9 is a powerful bioengineering tool used to modify genetic code in organisms. It can enhance an organism's performance or correct mutations by modifying its DNA.

How have scientists at Oak Ridge National Laboratory improved the CRISPR Cas9 tool?

The scientists at Oak Ridge National Laboratory have improved the CRISPR Cas9 tool by combining quantum biology, artificial intelligence (AI), and bioengineering. They developed a more accurate and reliable method for designing guide RNAs, which guide the Cas9 enzyme to the targeted site in the genome.

What were the limitations of the existing CRISPR Cas9 models?

The existing models for designing CRISPR Cas9 tools were primarily developed for mammalian cells and other model species, which led to weak and inconsistent efficiency when applied to microbes. This inconsistency was due to differences in chromosomal structures.

How did the scientists at ORNL address these limitations?

The ORNL scientists addressed these limitations by incorporating quantum biology into guide RNA design. They considered the quantum chemical properties of nucleotides to improve the effectiveness of the Cas9 enzyme-guide RNA complex binding with the microbe's DNA.

What is the AI model used by the researchers?

The researchers used an explainable AI model called iterative random forest. This model was trained on a dataset of approximately 50,000 guide RNAs and took into account the quantum properties of nucleotides. It provided insights into the molecular mechanisms underlying the efficiency of guide RNAs.

How did the researchers validate the AI model?

The researchers validated the AI model by performing CRISPR Cas9 cutting experiments on E. coli. They used guides selected by the model and conducted the experiments using the Summit supercomputer at ORNL.

What are the implications of the improved CRISPR Cas9 tools?

The improved CRISPR Cas9 tools have implications for a wide range of species, including humans. They can enhance the accuracy of targeted genetic modifications in drug development and contribute to functional genomics, allowing scientists to link genes to physical traits more effectively.

What are the future plans for the ORNL synthetic biology team?

The ORNL synthetic biology team plans to collaborate with computational science colleagues to further refine the microbial CRISPR Cas9 model. They aim to incorporate data from lab experiments and various microbial species to improve the predictability and precision of CRISPR technology.

What supported the research conducted by the ORNL team?

The research conducted by the ORNL team was supported by the Department of Energy's Genomic Science Program and the Center for Bioenergy Innovation.

How can these advancements benefit bioenergy production and bioenergy feedstock plants?

The advancements in CRISPR Cas9 technology can benefit bioenergy production and bioenergy feedstock plants by enabling more precise and efficient modifications of their DNA. This can lead to improved bioenergy production processes and enhanced characteristics in bioenergy feedstock plants.

Please note that the FAQs provided on this page are based on the news article published. While we strive to provide accurate and up-to-date information, it is always recommended to consult relevant authorities or professionals before making any decisions or taking action based on the FAQs or the news article.

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