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New molecule synthesis method could result in faster vaccine responses next pandemic

Scientists say their innovation will accelerate vaccine and other pharmaceutical responses to the next pandemic “by several orders of magnitude.”

(CN) — A team of scientists in Copenhagen has developed a tool they say will accelerate vaccine and other pharmaceutical responses to pandemics one million times over, while keeping costs at a minimum.

“The tool’s efficiency, reproducibility and absence of leakage may reduce material and time cost by several orders of magnitude compared with those of the current state of art,” according to research published Monday in Nature Chemistry.   

While searching for pharmaceutical agents, such as vaccines, industry workers routinely scan thousands of related prospective molecules. The new technique allows the process to unfold in as few as seven minutes, minimizing the use of energy and materials.

The method, through which 40,000 different molecules can be synthesized and analyzed within an area smaller than a pinhead, was developed through a highly interdisciplinary research effort in Denmark and will drastically reduce the amounts of material, energy and economic costs pharmaceutical companies expend, the researchers say.  

The method combines three separate elements: nanocontainers in the form of soap-like bubbles, DNA nanotechnology, which allows multiple ingredients to be mixed at once into the various soap bubble-like containers, and a methodology, such as FRET imaging or protein fingerprinting, to enable rapid protein identification, explained team head Nikos Hatzakis, a professor at Copenhagen University, in an email to Courthouse News.

The resulting solution is named “single particle combinatorial lipidic nanocontainer fusion based on DNA mediated fusion,” or SPARCLD for short.

SPARCLD’s power, researchers say, is based on a spatially resolved readout and miniaturization.

“The volumes are so small that the use of material can be compared to using one liter of water and one kilogram of material, instead of the entire volumes of water in all oceans, to test material corresponding to the entire mass of Mount Everest,” Hatzakis explained in a statement announcing the research.

“This is an unprecedented save in effort, material, manpower and energy,” Hatzakis added.

He said in an email to Courthouse News that for someone to try to reproduce the results gleaned by his team, though they were years in the making, would take only a few weeks at most.

“Saving infinite amounts of time, energy and manpower would be fundamentally important for any synthesis development and evaluation of pharmaceuticals,” Mette Malle, lead author on the study said in a press release.

The breakthrough builds on methodologies, technologies and expertise the team developed over years and involves integration of elements from disciplines that are ordinarily believed to be distant, including synthetic biochemistry, nanotechnology, DNA synthesis, combinational chemistry and artificial intelligence.

“No single element of our solution is new, but they have never been combined so seamlessly,” Hatzakis said.

“What we have is very close to a live read-out. This means that one can moderate the setup continuously based on the readings adding significant additional value. We expect this to be a key factor for industry wanting to implement the solution,” Malle explained in the release.

Although the researchers involved in the project have several industry collaborations underway, they don’t yet know which companies may want to use their method, as they’ve had to keep their data under wraps.

“We had to keep things hush-hush since we didn’t want to risk for others to publish something similar before us,” Hatzakis explained. “Thus, we could not engage in conversations with industry or with other researchers that may use the method in various applications.”

But he has some possible applications in mind.

“A safe bet would be that both industry and academic groups involved in synthesis of long molecules such as polymers could be among the first to adopt the method,” Hatzakis said in a press release. “The same goes for ligands of relevance for pharmaceutical development. A particular beauty of the method that it can be integrated further, allowing for direct addition of a relevant application.”

Examples of what Herzakis described could be RNA strings for the important biotech tool CRISPR, or an alternate for screening and detecting and synthesizing RNA for future pandemic vaccines.

“Our setup allows for integrating SPARCLD with post-combinatorial readout for combinations of protein-ligand reactions such as those relevant for use in CRISPR. Only, we have not been able to address this yet, since we wanted to publish our methodology first,” Hatzakis said.

The work was a collaboration between the Hatzakis Group, University of Copenhagen and the University of Southern Denmark. Additional support came from a Villum Foundation Center of Excellence grant.

Hatzakis said in his email that the research was not long in the making.

“What always takes long in science is the meticulous repetition of experiment, and the multiple control experiments to ensure the validity of the results,” he said.

Including the hard work of “extremely talented” Ph.D. students, of writing the manuscript, going through peer revision by other scientists and through the editorial correction of the journal, the research took just just three years, Hatzakis said.

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