Science & Technology

A new way to generate synthetic DNA

3D model of DNA. Credits: Michael Ströck / Wikimedia / GNU Free Documentation License

Chemically synthesized short DNA sequences are a very important component and have countless uses in laboratories, hospitals, and the industry, such as how to identify COVID-19. Phosphoramidite is a necessary component for the generation of DNA sequences, but it is unstable and quickly breaks down. PhD Alexander Sandahl (Aarhus University, Professor Kurt Gothelf’s group) collaborates with researchers in Professor Troels Skrydstrup’s group to quickly and efficiently manufacture and streamline DNA just before using unstable building blocks. We have developed a new patented method. Manufacture.

The generated DNA sequence is also called an oligonucleotide. They are widely used in disease identification, oligonucleotide-based drug manufacturing, and several other medical and bioengineering applications.

High demand Oligonucleotide Therefore, the production of chemical products requires an efficient and automated method. This process relies on phosphoramidite, a compound that has the drawback of becoming unstable unless stored at the ideal -20 degrees Celsius.

Since the instruments used for DNA synthesis cannot cool phosphoramidite, it is inevitable that some of them will degrade after being added to the instrument.

Avoid unwanted degradation of key ingredients

Professor Kurt Gothelf and Professor Troels Skrydstrup have each led research groups in organic chemistry, working together to develop relatively simple and efficient technologies that can automate the production of phosphoramidite and integrate it directly into DNA synthesizers. It was.

This avoids both these manual synthesis, which typically takes up to 12 hours, and the problem of unstable phosphoramidite storage. Gothelf’s group provided expertise in automated DNA synthesis, and Skrydstrup’s group provided know-how in chemical reactions (flow chemistry) that occur in continuously flowing liquids.

“This is a very rewarding collaboration and one of iNANO’s core values,” says Kurt Gothelf. “Also, much of the success of this project is due to Alexander Sandahl. He established a collaboration and developed and realized most of the project’s ideas.”

The results have just been published in the journal Nature Communications..

In the method of producing phosphoramidite, the nucleoside (starting material) is washed away through the solid substance (resin). It has the potential to be fully integrated into the automated process of instruments for DNA synthesis. The resin ensures that the nucleosides are rapidly phosphorylated, which converts the nucleosides to phosphoramidite within minutes. From the resin, phosphoramidite is automatically flushed to the part of the device responsible for DNA synthesis.

This allows phosphoramidite to be first produced (on demand) just before it is used, thus providing phosphoramidite in a faster and more efficient flow-based method that could be automated and manipulated by non-chemists. You can avoid the decomposition of amidite.

The first biocatalytically produced RNA basic building block

For more information:
Alexander F. Sandar et al., On-demand synthesis of phosphoramidite, Nature Communications (2021). DOI: 10.1038 / s41467-021-22945-z

Provided by
Aarhus University

Quote: Https: // New method for generating synthetic DNA obtained on May 12, 2021 (May 12, 2021)

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A new way to generate synthetic DNA A new way to generate synthetic DNA

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