Nature sub-newsletter breakthrough: "DNA origami" to determine the rules of vaccine design, nano-vaccine is expected to treat COVID-19 and other diseases!

, July 2, 2020 /
PRNewswire// By folding DNA into a virus-like structure, researchers at the Massachusetts Institute of Technology have designed an HIV-like particle that stimulates a strong immune response from human immune cells that grow in laboratory dishesThese particles may end up being used as an HIV vaccinethese DNA particles are very similar in size and shape to viruses, covered with HIV proteins or antigens, and are arranged in precise ways to stimulate a strong immune responseResearchers are currently working to adapt this approach to develop a potential SARS-CoV-2 vaccine that they expect to be used in a variety of viral diseases"
The rough design rules that this work began to produce should be generally applied to disease antigens and diseases," said Darrell Irvine, a Professor underwood-Prescott in the Department of Bioengineering and Materials Science and Engineering who is deputy director of miter's Koch Institute for Integrated Cancer research and a member of the Ragon Institute at MGH, MIT and HarvardPhoto Source: Nature Nanotechnology
Professor Mark Bathe, a professor of bioengineering at the Massachusetts Institute of Technology and a member of the Broad Institute at MIT and Harvard University, is the senior author of the study, which was recently published in Nature NanotechnologyThe paper's lead authors are former MIT postdoctoral students R?mi Veneziano and Tyson MoyerDNA design
because DNA molecules are highly programmable, and since the 1980s, scientists have been working on ways to design DNA molecules for drug delivery and many other fields, most recently using a technique called DNA origami, invented in 2006 by Paul Rothemund of the California Institute of Technology2016, Bathe's lab developed an algorithm that can automatically design and build arbitrary 3D virus shapes using DNA origamiThis method provides precise control over the structure of synthetic DNA, allowing researchers to attach molecules such as viral antigens to specific locations"The DNA structure is like a nail plate, and antigens can be attached to any position," Bathe said"These viral particles are now the first to reveal the fundamental molecular principles of immune cell recognition."natural viruses arenano-
particles where antigens are arranged on the surface of particles, and it is thought that the immune system (especially B cells) has evolved to effectively identify this particle antigenVaccines are being developed to mimic natural viral structures, and thisnano-
vaccine is considered very effective in producing an immune response of B cells because they have the correct size of the lymphatic tube, which can send them directly to the B cells in the lymph nodesThe size of these particles is also suitable for interaction with B cells and can present dense arrays of viral particles, however, determining the correct particle size, spacing between antigens, and the number of each particle antigen to optimally stimulate B cells (through its B-cell receptors in combination with the target antigen) has always been a challengeBathe and Irvine began using these DNA stents to simulate the granule structure of viruses and vaccines, hoping to discover the best granule design for activating B cells"There is interest in the use of viral-like particle structures that place vaccine antigens on the particle surface to stimulate the best B-cell response,"Irvine saidHowever, the rules of how to design this structure are not well understood"
other researchers have tried to make sub-vaccines with other types of synthetic particles, such as polymers, lipids, or self-assembled proteins, they do not control the location of viral proteins as precisely as DNA origami."in the study, researchers designed twenty-day particles of similar size and shape to a typical virusThey attached an engineered HIV antigen associated with the gp120 protein to the stent at different distances and densities To their surprise, they found that the vaccinethate that produces the strongest B-cell response is not necessarily one that wraps the antigen as tightly as possible on the surface of the stent people generally think that the higher the antigen density, the better, think that keeping B-cell receptors as close as possible is the driving reason for signaling However, the results are clear that the closest distance researchers can make is not the best Also, when the distance between the two antigens is widened, the signal transmission increases the results of this study are likely to guide the development of HIV vaccines, as the HIV antigens used in these studies are currently being tested in human clinical trials using proteins nano-
granule stents Based on their data, MIT researchers, in collaboration with Jayajit Das, a professor of immuno
logy and microbiology at Ohio State University, developed a model to explain why the farther the antigen is, the better the results When the antigen binds to the receptor on the surface of the B cell, the activated receptors cross-link with each other within the cell to enhance the response However, the model shows that if the antigen is too close, the reaction will weaken photo source: Nature Nanotechnology other diseases other than AIDS
In recent months, Bathe Labs has worked with Aaron and Daniel Schmidt, of the Ragon Institute, to create a variant of the vaccine, replacing HIV antigens with a protein on the surface of the SARS-CoV-2 virus They are currently testing isolated B cells and mice to test whether the vaccine can respond effectively to the SARS-CoV-2 coronavirus "Our platform technology allows you to easily swap different subgenic antigens and peptides from different types of viruses to test their potential vaccine capabilities," Bathe said researchers say that because this method allows antigens from different viruses to carry on the same DNA stents, it is possible to design variants for multiple coronaviruses, including past and future variants (BiovalleyBioon.com) references: Engineers use 'DNA origami' to identify design rules
Role of the nanoscale antigen organization on B-cell activation probed dd using DNA origami, Nature Nanotechnology (2020) DOI: 10.1038/s41565-020-0719-0 ,