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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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German Researchers Develop DNA Origami That Traps and Neutralizes Certain Viruses

This “Virus Trap” might eventually be manufactured by clinical laboratories for the diagnostic process

Clinical laboratory managers and pathologists will be fascinated by this new treatment coming out of Germany for viral infections. It’s an entirely different technology approach to locating and neutralizing live viruses that may eventually be able to control anti-viral-resistant strains of specific viruses as well.

As virologists and microbiologists are aware, even in our present era of technological and medical advances, viral infections are extremely difficult to treat. There are currently no effective antidotes against most viral infections and antibiotics are only successful in fighting bacterial infections.

Thus, this new technology developed by a research team at the Technical University of Munich (TUM) in Munich, Germany, that uses DNA origami to neutralize and trap viruses and render them harmless is sure to gain swift attention, especially given the world’s battle with the SARS-CoV-2 Omicron variant.

The researchers published their findings in the peer-reviewed journal Nature Materials, titled, “Programmable Icosahedral Shell System for Virus Trapping.”

Ulrike Protzer, MD

“Bacteria have a metabolism. We can attack them in different ways,” said virologist Ulrike Protzer, MD (above), Director of the Institute of Virology at TUM School of Medicine and one of the authors of the study, in a TUM press release. “Viruses, on the other hand, do not have their own metabolism, which is why antiviral drugs are almost always targeted against a specific enzyme in a single virus. Such a development takes time. If the idea of simply mechanically eliminating viruses can be realized, this would be widely applicable and thus an important breakthrough, especially for newly emerging viruses,” she added. (Photo copyright: Helmholtz Munich.)

Entrapping Viruses within 3D Hollow Structures

DNA origami is the nanoscale folding of DNA to create two- and three-dimensional complex shapes that can be manufactured with a high degree of precision at the nanoscale. Researchers have been working with and enhancing this technique for about 15 years.

However, scientists at TUM wondered if they could create such hollow structures based on the capsules that encompass viruses to entrap those viruses. They developed a method that made it possible to create artificial hollow bodies the size of a virus and explored using those hollow bodies as a type of “virus trap.”

The researchers theorized that if those hollow bodies could be lined on the inside with virus-binding molecules, they could tightly bind the viruses and remove them from circulation. For this method to be successful, however, those hollow bodies had to have large enough openings to ensure the viruses could get into the shells.

“None of the objects that we had built using DNA origami technology at that time would have been able to engulf a whole virus—they were simply too small,” said Hendrik Dietz, PhD, Professor of Physics at TUM and an author of the study in a press release. “Building stable hollow bodies of this size was a huge challenge,” he added.

So, the team of researchers used the icosahedron geometric shape, which is an object comprised of 20 sides. They engineered the hollow bodies for their virus trap from three-dimensional, triangular plates which had to have slightly beveled edges to ensure the binding points would assemble properly to the desired objects. 

“In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates,” Dietz explained. “We can now produce objects with up to 180 subunits and achieve yields of up to 95%. The route there was, however, quite rocky, with many iterations.”

By varying the binding points on the edges of the triangles, the scientists were able to create closed hollow spheres and spheres with openings or half-shells that could be utilized as virus traps. They successfully tested their virus traps on adeno-associated viruses (AAV) and hepatitis B viruses in cell cultures.

“Even a simple half-shell of the right size shows a measurable reduction in virus activity,” Dietz stated in the press release. “If we put five binding sites for the virus on the inside—for example suitable antibodies—we can already block the virus by 80%. If we incorporate more, we achieve complete blocking.”

The team irradiated their finished building blocks with ultraviolet (UV) light and then treated the outside with polyethylene glycol and oligolysine. This process prevented the DNA particles from being immediately degraded in body fluids. Those particles were stable in mouse serum for 24 hours. The TUM scientists plan to test their building blocks on living mice soon.

“We are very confident that this material will also be well tolerated by the human body,” Dietz said.

Could Clinical Laboratories Manufacture Components of the Virus Traps?

The researchers noted that the starting materials for their virus traps can be mass produced at a very reasonable cost and may have other uses. 

“In addition to the proposed application as a virus trap, our programmable system also creates other opportunities,” Dietz said. “It would also be conceivable to use it as a multivalent antigen carrier for vaccinations, as a DNA or RNA carrier for gene therapy, or as a transport vehicle for drugs.”

There is much research yet to be done on this cutting-edge technology. However, for this therapy to be appropriate for a patient, a specimen of the virus will need to be identified and studied. Then, the DNA origami would be tailored to capture that specific virus. Thus, it’s conceivable that clinical laboratories, if used for the diagnostic step, might also be able to then manufacture the virus trap that is customized to locate, surround, and neutralize that specific virus. 

JP Schlingman

Related Information:

Engineering a Virus Trap

Programmable Icosahedral Shell System for Virus Trapping

The Virus Trap

DNA Origami

DNA Origami Hits the Big Time

Custom-Size, Functional, and Durable DNA Origami with Design-Specific Scaffolds

Neutralizing Viruses with DNA Origami Traps

ProteomeTools Researchers Announces Milestone Creation of 330,000-Peptide Human Proteome and Creating Resource for Developing New Medical Laboratory Tests

Project should provide treasure-trove of molecular information on human protein and lead to development of new biomarkers for use in clinical laboratory tests and personalized medicine

Human proteins provide clinical laboratories and anatomic pathology groups with a rich source of biomarkers used in medical tests and personalized medicine. Pathologists, therefore, should take note of a major milestone achieved by researchers from the Technical University of Munich (TUM) that moves science closer to developing a way to understand the complete human proteome.

Scientists participating in the ProteomeTools project have announced the synthesis of a library of more than 330,000 peptides representing essentially all canonical proteins of the human proteome.

Translating Human Proteome into Molecular and Digital Tools

The ProteomeTools project is “a joint effort of TUM, JPT Peptide Technologies, SAP SE, and Thermo Fisher Scientific … dedicated to translating the human proteome into molecular and digital tools for drug discovery, personalized medicine, and life science research.” Over the course of the project, 1.4 million synthetic peptides covering essentially all human gene products will be synthesized and analyzed using multimodal liquid chromatography-tandem mass spectrometry (LC-MS/MS).

ProteomeTools published their first paper, “Building ProteomeTools Based on a Complete Synthetic Human Proteome,” which detailed their work in Nature Methods.

“ProteomeTools was started as a collaborative effort bringing together academic and industrial partners to make important contributions to the field of proteomics. It is gratifying to see that this work is now producing a wealth of significant results,” stated TUM researcher Bernhard Kuster, PhD, one of the leaders of the effort and senior author on the Nature Methods paper, in a TUM news release.

Thousands of New Biomarkers for Clinical Laboratories, and More!

Kuster discussed the significance of the consortium’s work in an article published in Genome Web, which described ProteomeTools as “a resource that provides the proteomics community with a set of established standards against which it can compare experimental data.”

“In proteomics today, we are doing everything by inference,” Kuster stated to Genome Web. “We have a tandem mass spectrum and we use a computer algorithm to match it to a peptide sequence that [is generated] in silico to simulate what their spectrum might look like without us actually knowing what it looks like. That is a very fundamental problem.”

Bernhard Kuster, PhD

Bernhard Kuster, PhD (above center), of the Technical University of Munich (TUM), led a team of researchers from the ProteomeTools project who completed a tandem mass spectrometry analysis of more than 330,000 synthetic tryptic peptides representing essentially all of the canonical human gene products. The resource eventually will cover all one million peptides. (Photo copyright: Andreas Heddergott/TUM.)

In the Genome Web article, Kuster provides an example of how researchers could use the information developed by ProteomeTools, noting it could be useful for confirming peptide identification in borderline cases. “Because the spectra for these synthetic peptides are available to everyone, you could look up a protein or peptide ID that you find exciting, but where the [experimental] data might not totally convince you as to whether it is true or not,” he explained.

Kuster also states that he believes the resource has the potential to allow “the field to move away from conventional database searching methods toward a spectral matching approach.”

The TUM news release notes that the ProteomeTools project “will generate a further one million peptides and corresponding spectra with a focus on splice variants, cancer mutations, and post-translational modifications, such as phosphorylation, acetylation, and ubiquitinylation.” The end result could be a treasure-trove of molecular information on the human proteome and development of thousands of new biomarkers for clinical use for therapeutic drugs, and more.

“Representing the human proteome by tandem mass spectra of synthetic peptides alleviates some of the current issues with protein identification and quantification. The libraries of peptides and spectra now allow us to develop new and improve upon existing hardware, software, workflows, and reagents for proteomics. Making all the data available to the public provides a wonderful opportunity to exploit this resource beyond what a single laboratory can do. We are now reaching out to the community to suggest interesting sets of peptides to make and measure as well as to create LC-MS/MS data on platforms not available to the ProteomeTools consortium,” Kuster stated in the TUM news release.

All data from the ProteomeTools project is available at the ProteomeXchange Consortium. Pathologists and clinical laboratory professionals working to develop new assays will find it to be a valuable resource.

—Andrea Downing Peck

Related Information:

Researchers Build Complete Synthetic Human Proteome

Building Proteome Tools Based on a Complete Synthetic Human Proteome

Milestone for the Analysis of Human Proteomes

New In Vivo Implant Device Monitors Tumor Growth Remotely

Clinical laboratory directors and pathologists will see threats and opportunities as microelectronic devices offer new diagnostic and therapeutic modalities

In vivo clinical diagnostic testing just took a giant step forward. A team of medical engineers at the Technical University of Munich  (TUM) have developed a prototype microchip sensor implant designed to continuously monitor tumors remotely.

Internal Detection Device Allows For Remote Monitoring In Real Time

The device, called IntelliTuM (Intelligent Implant for Tumor Monitoring), detects the level of dissolved oxygen in the fluid near the tumor, according to an online article at Technology Review, published by Massachusetts Institute of Technology.