A new tool speeds up development of vaccines and other pharmaceutical
products by more than 1 million times while minimizing costs.
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 journal Nature Chemistry.
More than 40,000 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," says head of the team Nikos Hatzakis, Associate
Professor at the Department of Chemistry, University of Copenhagen.
"Saving infinitely [on] amounts of time, energy and manpower would be
fundamentally important for any synthesis development and evaluation of
pharmaceuticals," says Ph.D. Student Mette G. Malle, lead author of the
article, and currently Postdoc researcher at Harvard University, U.S..
Results within just seven minutes
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
distant disciplines: synthetic biochemistry, nanotechnology, DNA synthesis,
combinational chemistry, and even Machine Learning, which is an AI
(artificial intelligence) discipline.
"No single element in our solution is completely new, but they have never
been combined so seamlessly," explains Nikos Hatzakis.
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 G. Malle.
'Had to keep things hush-hush'
The individual researchers in the project have several industry
collaborations, yet they do not 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 [is] 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."
Reference:
Malle, M.G., Löffler, P.M.G., Bohr, S.SR. et al. Single-particle combinatorial
multiplexed liposome fusion mediated by DNA. Nat. Chem. (2022).
DOI: 10.1038/s41557-022-00912-5