By folding DNA into a virus-like structure, MIT researchers have designed HIV-like particles that provoke a strong immune response from human immune cells grown in a lab dish. Such particles might eventually be used as an HIV vaccine.
The DNA particles, which closely mimic the size and shape of viruses, are coated with HIV proteins, or antigens, arranged in precise patterns designed to provoke a strong immune response. The researchers are now working on adapting this approach to develop a potential vaccine for SARS-CoV-2, and they anticipate it could work for a wide variety of viral diseases.
The rough design rules that are starting to come out of this work should be generically applicable across disease antigens and diseases, says Darrell Irvine, who is the Underwood-Prescott Professor with appointments in the departments of Biological Engineering and Materials Science and Engineering; an associate director of MITs Koch Institute for Integrative Cancer Research; and a member of the Ragon Institute of MGH, MIT, and Harvard.
Irvine and Mark Bathe, an MIT professor of biological engineering and an associate member of the Broad Institute of MIT and Harvard, are the senior authors of the study, which appears today inNature Nanotechnology. The papers lead authors are former MIT postdocs Rmi Veneziano and Tyson Moyer.
DNA design
Because DNA molecules are highly programmable, scientists have been working since the 1980s on methods to design DNA molecules that could be used for drug delivery and many other applications, most recently using a technique called DNA origami that was invented in 2006 by Paul Rothemund of Caltech.
In 2016, Bathes lab developed an algorithm that can automatically design and build arbitrary three-dimensionalvirus-like shapesusing DNA origami. This method offers precise control over the structure of synthetic DNA, allowing researchers to attach a variety of molecules, such as viral antigens, at specific locations.
The DNA structure is like a pegboard where the antigens can be attached at any position, Bathe says. These virus-like particles have now enabled us to reveal fundamental molecular principles of immune cell recognition for the first time.
Natural viruses are nanoparticles with antigens arrayed on the particle surface, and it is thought that the immune system (especially B cells) has evolved to efficiently recognize such particulate antigens. Vaccines are now being developed to mimic natural viral structures, and such nanoparticle vaccines are believed to be very effective at producing a B cell immune response because they are the right size to be carried to the lymphatic vessels, which send them directly to B cells waiting in the lymph nodes. The particles are also the right size to interact with B cells and can present a dense array of viral particles.
However, determining the right particle size, spacing between antigens, and number of antigens per particle to optimally stimulate B cells (which bind to target antigens through their B cell receptors) has been a challenge. Bathe and Irvine set out to use these DNA scaffolds to mimic such viral and vaccine particle structures, in hopes of discovering the best particle designs for B cell activation.
There is a lot of interest in the use of virus-like particle structures, where you take a vaccine antigen and array it on the surface of a particle, to drive optimal B-cell responses, Irvine says. However, the rules for how to design that display are really not well-understood.
Other researchers have tried to create subunit vaccines using other kinds of synthetic particles, such as polymers, liposomes, or self-assembling proteins, but with those materials, it is not possible to control the placement of viral proteins as precisely as with DNA origami.
For this study, the researchers designed icosahedral particles with a similar size and shape as a typical virus. They attached an engineered HIV antigen related to the gp120 protein to the scaffold at a variety of distances and densities. To their surprise, they found that the vaccines that produced the strongest response B cell responses were not necessarily those that packed the antigens as closely as possible on the scaffold surface.
It is often assumed that the higher the antigen density, the better, with the idea that bringing B cell receptors as close together as possible is what drives signaling. However, the experimental result, which was very clear, was that actually the closest possible spacing we could make was not the best. And, and as you widen the distance between two antigens, signaling increased, Irvine says.
The findings from this study have the potential to guide HIV vaccine development, as the HIV antigen used in these studies is currently being tested in a clinical trial in humans, using a protein nanoparticle scaffold.
Based on their data, the MIT researchers worked with Jayajit Das, a professor of immunology and microbiology at Ohio State University, to develop a model to explain why greater distances between antigens produce better results. When antigens bind to receptors on the surface of B cells, the activated receptors crosslink with each other inside the cell, enhancing their response. However, the model suggests that if the antigens are too close together, this response is diminished.
Beyond HIV
In recent months, Bathes lab has created a variant of this vaccine with the Aaron Schmidt and Daniel Lingwood labs at the Ragon Institute, in which they swapped out the HIV antigens for a protein found on the surface of the SARS-CoV-2 virus. They are now testing whether this vaccine will produce an effective response against the coronavirus SARS-CoV-2 in isolated B cells, and in mice.
Our platform technology allows you to easily swap out different subunit antigens and peptides from different types of viruses to test whether they may potentially be functional as vaccines, Bathe says.
Because this approach allows for antigens from different viruses to be carried on the same DNA scaffold, it could be possible to design variants that target multiple types of coronaviruses, including past and potentially future variants that may emerge, the researchers say.
Reference: Veneziano et al. (2020). Role of nanoscale antigen organization on B-cell activation probed using DNA origami. Nature Nanotechnology. DOI: 10.1038/s41565-020-0719-0.
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
Original post:
Rewriting the Rules of Vaccine Design With DNA Origami - Technology Networks
- Protein folding - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: September 11th, 2019]
- Protein Folding: The Good, the Bad, and the Ugly - Science ... [Last Updated On: August 18th, 2024] [Originally Added On: September 13th, 2019]
- Protein Folding - Chemistry LibreTexts [Last Updated On: August 18th, 2024] [Originally Added On: September 14th, 2019]
- Protein Structure and Folding [Last Updated On: August 18th, 2024] [Originally Added On: September 19th, 2019]
- Structural Biochemistry/Proteins/Protein Folding ... [Last Updated On: August 18th, 2024] [Originally Added On: September 28th, 2019]
- Proteopathy - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: October 1st, 2019]
- Folding@home - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: October 1st, 2019]
- Denaturation and Protein Folding | Introduction to Chemistry [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Folding - Anfinsen's Experiment ~ Biology Exams 4 U [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Structures: Primary, Secondary, Tertiary, Quaternary ... [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Folding - an overview | ScienceDirect Topics [Last Updated On: August 18th, 2024] [Originally Added On: October 6th, 2019]
- Thermodynamics of spontaneous protein folding: role of ... [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- Molecular Biology 02: 'Thermodynamics of protein folding' [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- The Science Behind Foldit | Foldit [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- Diseases Folding@home [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- DeepMind timeline: The history of the UK's pioneering AI firm - Techworld.com [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Geroscience and it's Impact on the Human Healthspan: A podcast with John Newman - GeriPal - A Geriatrics and Palliative Care Blog [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Yumanity Therapeutics Initiates Phase 1 Clinical Trial of Lead Candidate YTX-7739 for the Treatment of Parkinson's Disease | Small Molecules | News... [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Tenure-Track or Tenure-Eligible Position in the Laboratory of Chemical Physics job with National Institutes of Health | 28302 - Chemical &... [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Food for the soul: Traditional gyza makers and eaters in Utsunomiya try to keep the dumplings rolling - The Japan Times [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- UT molecular evolution professor named 2019 American Physical Society Fellow - UT The Daily Texan [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- 9 must-have Instant Pot accessories for healthy eating - CNET [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Researchers Find Fish Wearing Natural 'Bullet-Proof Vest' to Thwart Piranhas in Amazon - News18 [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Christopher Dobson: chemist whose work on proteins advanced research into neurodegenerative diseases - The BMJ [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Two years in the making, Pizza Hut tests a round pizza box - Fast Company [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Fava Is All About Balance - East Bay Express [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Amazon fish wears nature's 'bullet-proof vest' to thwart piranhas - Reuters [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- RNA Folding Insights Lead to New Therapeutics and Synthetic Biology Technologies - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- The Hidden Inactive Ingredient: Biological Products in Recombinant Pharmaceuticals - P&T Community [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Insights into Parkinson's Onset May Lie in New Model of Cell Aging and Damage - Parkinson's News Today [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Antibiotics with novel mechanism of action discovered - Drug Target Review [Last Updated On: August 18th, 2024] [Originally Added On: October 25th, 2019]
- The top AI lighthouse projects to watch in biopharma - FierceBiotech [Last Updated On: August 18th, 2024] [Originally Added On: October 25th, 2019]
- UCI vision scientist Krzysztof Palczewski elected to National Academy of Medicine - UCI News [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- Rett Syndrome Tied to Altered Protein Levels in Brain in Early Study - Rett Syndrome News [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- Bulls-Eye: Imaging Technology Could Confirm When a Drug Is Going to the Right Place - On Cancer - Memorial Sloan Kettering [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- Discover: Science is often wrong and that's actually a really good thing - Sudbury.com [Last Updated On: August 18th, 2024] [Originally Added On: November 2nd, 2019]
- IBM vs. Google and the Race to Quantum Supremacy - Citizen Truth [Last Updated On: August 18th, 2024] [Originally Added On: November 7th, 2019]
- Microprotein ID'd Affecting Protein Folding and Cell Stress Linked to Diseases Like Huntington's, Study Finds - Huntington's Disease News [Last Updated On: August 18th, 2024] [Originally Added On: November 7th, 2019]
- IBM vs. Google and the race to quantum supremacy - Salon [Last Updated On: August 18th, 2024] [Originally Added On: November 11th, 2019]
- That Junk DNA Is Full of Information! - Advanced Science News [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- Argonne Researchers to Share Scientific Computing Insights at SC19 - HPCwire [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- How to Make the Most of Your Old Tech - New York Magazine [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- 2 tricked-out pies to be thankful for: pear with cranberries and pumpkin with ginger praline - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: November 17th, 2019]
- From Mediterranean Lentil Salad to Cinnamon Raisin Bread: Our Top 10 Vegan Recipes of the Day! - One Green Planet [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- What is Biophysical Analysis? - The John Innes Centre [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- Thermodynamic probes of instability: application to therapeutic proteins - European Pharmaceutical Review [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- In science, its better to be curious than correct - The Conversation CA [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- New Study Reveals US Airlines With the Healthiest Food Options - TravelPulse [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- Study Reveals Hepatitis A Originated in Insects - Advanced Science News [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- How Home-Baked Bread Is Defying the Industrial Food System - YES! Magazine [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- Black Friday Is Absolutely Massive. Here Are a Bunch of Deals We Couldn't Call Out Individually - Gear Patrol [Last Updated On: August 18th, 2024] [Originally Added On: November 30th, 2019]
- A conserved ATP- and Scc2/4-dependent activity for cohesin in tethering DNA molecules - Science Advances [Last Updated On: August 18th, 2024] [Originally Added On: November 30th, 2019]
- Ancient Worm Reveals Way to Destroy Toxic Cells Potential New Therapy for Huntingtons and Parkinsons - SciTechDaily [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Biologics Market Size Expand at a CAGR of 3.9 With $399.5 Billion By 2025 - MENAFN.COM [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Exploring the Diversity of Parkinson's Proteins - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Early detection of brain degeneration on the horizon with innovative sensor - UNM Newsroom [Last Updated On: August 18th, 2024] [Originally Added On: December 16th, 2019]
- Holiday cookies from around the world | Features - yoursun.com [Last Updated On: August 18th, 2024] [Originally Added On: December 22nd, 2019]
- The Art of Origami is Now A Key Tool That Helps Doctors Save Lives - Nature World News [Last Updated On: August 18th, 2024] [Originally Added On: December 23rd, 2019]
- Nanopores can identify the amino acids in proteins, the first step to sequencing - University of Illinois News [Last Updated On: August 18th, 2024] [Originally Added On: December 23rd, 2019]
- Wow your New Year's Eve guests with a puff pastry appetizer - KARE11.com [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- The 10 most compelling product innovations of 2019 - Fast Company [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Our best recipes from 2019 | Food and cooking - STLtoday.com [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- The best WIRED long reads of 2019 - Wired.co.uk [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Structure of Drosophila melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag - Science Advances [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Gocycle to partner with nutrition brand Fuel10k to promote benefits of e-bikes - Bike Biz [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- The Importance of Understanding TargetProtein Interactions in Drug Discovery - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- How DeepMind is unlocking the secrets of dopamine and protein folding with AI - VentureBeat [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- How To Grow (Almost) Anything - Hackaday [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- U of T's Peter Wittek, who will be remembered at Feb. 3 event, on why the future is quantum - News@UofT [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- The DeepMind algorithm to solve two complex problems of biology - The Times Hub [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- High Focus on Product Innovation & Development to Assist the Growth of the Folding Cartons Market between and . 2017 2025 Dagoretti News -... [Last Updated On: August 18th, 2024] [Originally Added On: January 24th, 2020]
- Folded, frozen, and faster: JUST Egg is now more convenient, and cheaper, to enjoy - FoodNavigator-USA.com [Last Updated On: August 18th, 2024] [Originally Added On: January 24th, 2020]
- Phyllo, cheese, heaven: Balkan women have been making these treats for centuries - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: January 26th, 2020]
- Phyllo, cheese, heaven: Balkan women have been making these treats for centuries - Waterbury Republican American [Last Updated On: August 18th, 2024] [Originally Added On: January 28th, 2020]
- The keto diet: Its highs and lows plus 5 recipes - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: February 12th, 2020]
- Study Shows How Soap Molecules Alter the Protein Structure - AZoM [Last Updated On: August 18th, 2024] [Originally Added On: February 12th, 2020]
- CryoEM of CBD Tau Suggests Another Unique Protofibril - Alzforum [Last Updated On: August 18th, 2024] [Originally Added On: February 16th, 2020]
- Working In Science Was A Brutal Education. Thats Why I Left. - BuzzFeed News [Last Updated On: August 18th, 2024] [Originally Added On: February 17th, 2020]
- The Evolution of the Eye, Demystified - Discovery Institute [Last Updated On: August 18th, 2024] [Originally Added On: February 28th, 2020]
- L-serine could be used to treat ALS, after promising study results - Drug Target Review [Last Updated On: August 18th, 2024] [Originally Added On: February 28th, 2020]