Revolutionary tool will meet future pandemics with accelerated response.
A new tool speeds up development of vaccines and other pharmaceutical products by more than one 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 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.
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 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.”
The scientific article on SPARCLD will be published in the prestigious journal Nature Chemistry on April 4, 2022.
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.
Reference: “Single-particle combinatorial multiplexed liposome fusion mediated by DNA” 4 April 2022, Nature Chemistry.
Very Interesting.Some Thoughts.
1. Process innovation is always far better than Product innovation.
2. Important to relaize that interdisciplinary research is extremely critical to achieve breakhroughts. This means genuine sharing of knowledge across artifical borders and man-made barriers for sharing of knowledge, to enable all of us to make the world slighty better.
3. The Virus will breach the blood-brain quicker than human beings greed for a fatter bank balance, which by-the-way none of which, they can take with them when the soul leaves the body on its endless journey!!
4. The enitire infrastructure of knowledge creation and sharing is based on the principle of Greed is Good and Competitive forces are best at allocation of scarce resuorces. Both are Sound in principle for humn activity but flawed in practise. Why do I say this?
5. The question is Greed for what? If it is oly monetary wealth it appears highly flawed to me. There are many other more important things like new knowledge, “doing the maximum Good for Maximum number in the global population” , and other strategic objectives like survival of the HUman Species etc.
6. It is true tht Competirive forces are the most efficient source for allocation of scarce resources. However, one of the scarcest resource is common sense! Don’t think that competitive forces have been effective as is evident in the curret ongoing conflict we are watching. Competition needs to be moderated and managed in times of existential crisis, like the recent pandemic we hve been through in recent times and other unexpected black swan events.
7. Coming to the findings described in the methodology described above. One word describes it, best. Brilliant. Some additional thoughts for consideration.
a. How do we traanslate such breakthroughs in methodology, to make the same available widely for the maximum beefit for maximum population globaally in the shortest timeframe?
(1) Use the mainframe to Personal Computer (MPC) availability model to drive down costs and ensure accessibility at lowest unit level.
(2) This MPC model implies that we increase the potential for use/misuse of such technologies eight billion to ten billion fold.
b. MISUSE can be controled in this type of case by ensure using of Sensor Technologis on Steroids.
Last word. Watch the sunlight reflect the colours of the rainbow inside a soap bubble and explain what role light plays in this procesws/methodology plays. I am sure that this “Revolutionary DNA Nano-technology ” was not carried out in a environment free of air, light, dust and other natural substances! Regardless– it is indeed a breakthrough. Congratulations.
Views expressed are personal and not binding o anyone!