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Revolutionary DNA Nanotechnology Speeds Up Development of Vaccines by More Than One Million Times:

In search of pharmaceutical agents such as new vaccines, industry will routinely scan thousands of related candidate molecules. A novel technique allows this to take place on the nano scale, minimizing use of materials and energy. The work is published in the prestigious journal Nature Chemistry.

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, promises to drastically reduce the amounts of material, energy, and economic cost for pharmaceutical companies.

The method works by using soap-like bubbles as nano-containers. With DNA nanotechnology, 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 the entire volumes of water in all oceans to test material corresponding to the entire mass of Mount Everest. This is an unprecedented save in effort, material, manpower, and energy," illustrates head of the team Nikos Hatzakis, Associate Professor at the Department of Chemistry, University of Copenhagen.

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

[...] The SPARCLD method (single particle combinatorial lipidic nanocontainer fusion based on DNA mediated fusion) is a parallelized, multi-step and non-deterministic fusion of individual zepto-liter nano-containers. The research team has observed efficient (more than 93 %) leakage-free fusion sequences for arrays of surface tethered target liposomes with six freely diffusing populations of cargo liposomes, each functionalized with individual lapidated DNA (LiNA) and fluorescent barcoded by distinct ratio of chromophores. Stochastic fusion results in distinct permutation of fusion sequences for each autonomous nano-container. Real-time total internal reflection (TIRF) microscopy allowed direct observation of more than 16,000 fusions and accurate classification of 566 distinct fusion sequences using Machine Learning. The method allows for approximately 42,000 nano-containers per square millimeter.

Journal Reference:
Malle, Mette Galsgaard, Löffler, Philipp M. G., Bohr, Søren S.-R., et al. Single-particle combinatorial multiplexed liposome fusion mediated by DNA, Nature Chemistry (DOI: 10.1038/s41557-022-00912-5)

Original Submission