A new DNA tool is speeding up vaccine development by a million fold

During the COVID-19 pandemic we could have done with a tool like this one, which could have let us produce vaccines in just seven minutes, even though ultimately the COVID-19 vaccines were developed multiple times faster than any other vaccines in history – in most cases cutting five to ten year development cycles down to just 3 months. In the latest development though a new tool developed by teams of researchers from around the world speeds up development of vaccines and other pharmaceutical products by more than one million times while minimizing costs.

When searching for pharmaceutical agents such as new vaccines companies will routinely scan thousands of related candidate molecules, but now a new technique lets this to take place on the nano scale and dramatically minimizes the use of materials and energy. The work is published in the prestigious journal Nature Chemistry.

Now more than 40,000 different molecules can be synthesized and analyzed within an area smaller than a pinhead. The method, developed through a highly interdisciplinary research effort in Denmark, works by using soap-like bubbles as nano-containers. Then, using DNA nano-technology multiple ingredients can be mixed within the containers.

“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 using the entire volumes of all the water in the oceans to test material corresponding to the entire mass of Mount Everest. This is an unprecedented saving in effort, material, manpower, and energy,” says Nikos Hatzakis, Associate Professor at the University of Copenhagen.

“Saving infinite amounts of time, energy and manpower would be fundamentally important for any synthesis development and evaluation of any future pharmaceuticals,” says PhD Student Mette G. Malle, lead author of the article, and currently Postdoc researcher at Harvard University.

The work has been carried out in collaboration between the Hatzakis Group, University of Copenhagen, and Associate Professor Stefan Vogel, University of Southern Denmark. The project has been supported by a Villum Foundation Center of Excellence grant. The resulting solution is named “single particle combinatorial lipidic nanocontainer fusion based on DNA mediated fusion” – abbreviated SPARCLD.

The breakthrough involves integration of elements from normally quite different disciplines: synthetic biochemistry, nanotechnology, DNA synthesis, combinational chemistry, and even Machine Learning which is an Artificial Intelligence (AI) discipline.

“No single element in our solution is completely new, but they have never been combined so seamlessly,” explains Nikos Hatzakis.

Crucially, the method provides results within just seven minutes.

“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,” says Mette Malle.

The individual researchers in the project have several industry collaborations, yet they don’t know which companies may want to implement the new high-throughput method.

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

Still, he can name some possible applications: “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. 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.”

Here, examples 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.”