Researchers CREATE Synthetic Chromosomes Faster and Cheaper

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A groundbreaking new technique invented by researchers at the USC Dornsife College of Letters, Arts and Science could revolutionize the field of synthetic biology. Known as CReATiNG (Cloning Reprogramming and Assembling Tiled Natural Genomic DNA), the method offers a simpler and more cost-effective way to create synthetic chromosomes. It will improve genetic engineering and enable a wide range of advances in medicine, biotechnology, biofuel production and even space exploration.

CREATing works by cloning and reassembling natural segments of DNA from yeast, allowing scientists to create synthetic chromosomes that can replace their native counterparts in cells. The new technique enables researchers to combine chromosomes between different yeast strains and species, alter chromosome structures, and delete multiple genes simultaneously.

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Lead researcher Ian Ehrenreich, professor of biological sciences at USC Dornsife, said the method is a major improvement over current technology. With CREATiNG, we can genetically reprogram organisms in complex ways that were previously considered impossible, even with new tools like CRISPR, he said. This opens up a world of possibilities in synthetic biology, advancing our fundamental understanding of life and paving the way for groundbreaking applications.

The study was published December 20 at Communication in Nature.

CREATing makes hard research easier, cheaper

The field of synthetic biology emerged as a way for scientists to control living cells, such as yeast and bacteria, to better understand how they work and to make useful compounds, such as new ones. medicine.

Over the past decade or so, a new form of synthetic biology has emerged called synthetic genomics, which involves synthesizing the entire chromosomes or entire genomes of organisms, Ehrenreich said. The thing about most synthetic genomics research is that it involves building chromosomes or genomes from scratch using chemically synthesized pieces of DNA. It’s a ton of work and very expensive.

However, there are no alternatives until now. CREATing offers the opportunity to use natural pieces of DNA as parts to assemble whole chromosomes, says Agilent postdoctoral fellow Alessandro Coradini, who studied with the first author.

The approach makes advanced genetic research more accessible by lowering costs and technical barriers so scientists can unlock new solutions to some of the most pressing challenges in science and medicine today.

CREATing can help in medicine, space exploration and more

The findings are particularly important for their potential applications in biotechnology and medicine. CREATing could lead to more efficient production of pharmaceuticals and biofuels, help develop cell therapies for diseases such as cancer and pave the way to environmental bioremediation methods, such as creating bacteria that consume of impurities.

The method may even extend to helping humans survive long periods in space or other harsh environments. Scientists may one day use CREATiNG to grow microorganisms or plants that can thrive on space stations or on long-distance space travel, although researchers warn that this will require more research in the future.

One of the most surprising aspects of the study, according to the researchers, is how rearranging parts of the yeast chromosome can change their growth rates, with some changes that result in a 68% faster or slower growth. This discovery highlights the profound impact that genetic structure can have on biological function and opens new avenues of research to further explore these relationships.

Reference: Coradini ALV, Ville CN, Krieger ZA, et al. Construct synthetic chromosomes from natural DNA. Nat Comm. 2023;14(1):8337. doi: 10.1038/s41467-023-44112-2

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