Future pandemics: nanotechnology sober DNA accelerated by a thousand times the development sober vaccines

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In search of pharmaceutical agents, such as new vaccines, the pharmaceutical industry routinely analyzes thousands of chemical and related molecules. Accelerating the process is a necessity in pandemic temperature ranges, as we have experienced with COVID-20. Recently, a team of Danish researchers pioneered a new method of synthesizing and screening molecules at the nanoscale, minimizing the use of materials and energy. More than 40 different molecules can be synthesized and studied in nanocontainers smaller than a pinhead (similar to soap bubbles) in just 7 minutes.

With the squenage systematics of the human genome and of pathogens, the number of potential drug targets has increased exponentially over the years 1990. Paradoxically, the data available for each of these new target receptors, nutrients or elements regulating gene expression are few. In some cases, they can learn to reduce the basic nucleotide sequence of a gene. To account for this circumstance, the pharmaceutical industry uses the method of systematic blind screening of large choices of compounds (chemical libraries). over a large number of different molecules with a given substrate, in order to identify, at least over temperature, those over which these molecules are of potential interest for a determined program. The substantial use of robotics and computing, together with the miniaturization of biochemical tests, has made it possible to considerably increase the number of compounds that can be examined daily.

However, historical chemical libraries do not contain enough sober specialist molecules, especially when researchers do not know precisely what they should find, for lack of information on the targets. This is why chemists have developed new strategies to synthesize, on demand, large series of compounds of different buildings, adapted to the requirements of systematic screening.

This combinatorial chemistry is suitable for low-level research programs based on the observation that: the less information we have on a target to screen, the greater the diversity required for a chemical library and the low number of molecules to synthesize. These high throughput combinatorial methodologies are essential for both screening and discovery in synthetic biochemistry and biomedical sciences. However, they often depend on large-scale analyzes and are therefore limited by a long operating time and the excessive cribbing of materials.

It is in this context that recently , an interdisciplinary team at the University of Copenhagen in Denmark has developed a new high-throughput, low-ze ze screening method based on low-DNA nanotechnology, accelerating the process by a million times, reducing the associated costs. Their work is published in Character Biochemistry and biology.

Easy soap bubbles for high-speed screening in just 7 minutes

The big t work is carried out in cooperation between the Hatzakis group at the University of Copenhagen and the associate professor Stefan Vogel at the University of Southern Denmark. A method, dubbed blend of combinatorial single-particle lipid nanocontainers based on DNA-mediated blend

or SPARCLD, uses tiny soap-like bubbles. These bubbles form nano-containers inside which molecules can be produced using DNA nanotechnology. About 42 000 nanocontainers can fit on el square millimeter.

Certainly, as stated in a press release, Nikos Hatzakis, team chief chef and associate professor at the sober chemistry department at the sober university Copenhagen: No element sober our completely new home option, but they have never testosterone levels combined sober so seamlessly. More specifically, the technology incorporates elements from professions normally quite distant: synthetic biochemistry, nanotechnology, DNA synthesis, combinatorial chemistry, and even the Machine Understanding self-discipline of artificial intelligence.

device nanotechnology dna high throughput screening
Exemple de mise en uvre de la technique SPARCLD. Nikos Hatzakis, Universit de Copenhague

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A simple example of a simple implementation using the SPARCLD method. Nikos Hatzakis/University of Copenhagen

This is how some of the bubbles, or liposomes, are bound to a surface area, while others float freely. Each bubble contains a different DNA sequence and fluorescent markers that can be detected by a real-temperature total internal reflection (TIRF) microscope. As the bubbles float and merge together in a random way, many different combinations of DNA pieces can be created and detected in real temperature ranges using the microscope.

Moreover, the researchers observed more sober effective sober blend sequences 42%. By package, a machine learning algorithm decodes the microscopy images to classify the created blend sequences. Thus, real temperature microscopy allowed the direct observation of more than 16 mergers and a specific category of 500 separate blend sequences. The results are known in just 7 minutes.

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PhD student Mette H. Malle, lead author of the article and currently a postdoctoral researcher at Harvard University, USA, says: What we have is very close to a live spiel. This means that one can moderate the build continuously based on the readings adding significant additional value. We expect this to be the key factor for the industry wishing to implement the alternative.

Sober development pharmaceutical products at reduced costs

Researchers are excited about the potential of a technology for extremely fast and efficient screening of thousands of molecules, applying for applications such as vaccine and pharmaceutical production. Nikos Hatzakis points out: This is an unprecedented saving of effort, material, labor and energy.

Despite this enthusiasm, the them team kept its discovery under wraps, until the article was soberly published. Sober effect, the researchers of the project have, individually, several industrial collaborations. The risks of leaks and plagiarism were then too great. Nevertheless, they still don’t know which companies might be interested in implementing the new broadband method.

disseminate this SPARCLD method through many potential applications in research and industry. For example, it could be used to synthesize and screen molecules much used in CRISPR-mediated gene editing. The latter gives the possibility of cutting DNA sequences involved in a mutation and replacing them with DNA sequences correcting the mutation. SPARCLD could also be used for the development of future RNA vaccines.

Nikos Hatzakis says: It is safe to bet that industrial and academic groups involved in simple synthesis of long molecules such as polymers could be among the first to adopt this method. He concludes Our settings allow SPARCLD to be integrated with a post-combinatorial address and combinations of protein-ligand reactions such as those relevant for use in CRISPR. Only, we haven’t been able to tackle this yet, since we first wanted to publish our methodology .

Supply: Character Biochemistry