DNA origami vaccines could be the next leap beyond mRNA
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DNA origami vaccines could be the next leap beyond mRNA
A next-generation DNA origami vaccine could rival mRNA shots while being easier to make and distribute.
Date:
March 17, 2026
Source:
Wyss Institute for Biologically Inspired Engineering at Harvard
Summary:
mRNA vaccines saved millions of lives during COVID-19 but have limitations like waning immunity and complex production. Scientists are now testing a new platform called DoriVac, which uses folded DNA nanostructures to better control how the immune system responds. In early studies, it produced strong antibody and T cell responses in both mice and human models. Researchers say it could lead to more stable, easier-to-manufacture vaccines for diseases like COVID-19, HIV, and Ebola.
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A new DNA origami vaccine platform called DoriVac could overcome key limitations of mRNA vaccines. Early tests show it triggers strong immune responses while being more stable and easier to produce. Credit: Shutterstock
The COVID-19 pandemic brought messenger RNA (mRNA) vaccines into the global spotlight. After completing clinical trials, the first COVID-19 mRNA vaccine was given on December 8, 2020. Researchers later estimated through modeling that these vaccines prevented at least 14.4 million deaths worldwide during their first year.
Because of their strong impact, scientists began developing mRNA vaccines for other infectious diseases. Ongoing clinical trials are targeting influenza virus, Respiratory Syncytial Virus (RSV), HIV, Zika, Epstein-Barr virus, and tuberculosis bacteria. At the same time, studies of COVID-19 vaccines have revealed important limitations, pointing to the need for new vaccine strategies.
Challenges With mRNA Vaccine Performance and Production
The immune protection generated by COVID-19 mRNA vaccines can differ widely from person to person, and the protection does not last indefinitely. This issue is made more difficult by the constant evolution of SARS-CoV-2, which produces new variants that can partially escape immune defenses. As a result, vaccines often need to be updated.
There are also practical challenges. Manufacturing mRNA vaccines is complex and expensive, and controlling how many mRNA molecules are packaged into lipid nanoparticles remains difficult. These vaccines also require cold storage and may cause unintended off-target effects. Overcoming these limitations could improve how the world prepares for and responds to future infectious disease threats.
DNA Origami Vaccine Platform Offers an Alternative
To address these issues, a multidisciplinary team from the Wyss Institute at Harvard University, Dana-Farber Cancer Institute (DFCI), and partner institutions explored a different approach. They used a DNA origami nanotechnology platform called DoriVac, which functions as both a vaccine and an adjuvant.
The researchers designed DoriVac vaccines to target a peptide region (HR2) found in the spike proteins of several viruses, including SARS-CoV-2, HIV, and Ebola. In mice, the SARS-CoV-2 HR2 vaccine triggered strong immune responses, including antibody-driven (humoral) and T cell-driven (cellular) activity.
The team also tested the vaccine in a preclinical human model using the Wyss Institute's microfluidic human Organ Chip technology, which simulates a human lymph node in vitro. In this system, the SARS-CoV-2 HR2 vaccine also generated strong antigen-specific immune responses in human cells.
When directly compared with SARS-CoV-2 mRNA vaccines delivered through lipid nanoparticles, a DoriVac vaccine carrying the same spike protein variant produced a similarly strong immune activation in human models. However, the DNA origami vaccine showed advantages in stability and was easier to store and manufacture. These findings were reported in Nature Biomedical Engineering.
"With the DoriVac platform, we have developed an extremely flexible chassis with a number of critical advantages, including an unprecedented control over vaccine composition, and the ability to program immune recognition in targeted immune cells on a molecular level to achieve better responses," said co-corresponding author and Wyss Institute Core Faculty member William Shih, Ph.D., whose group pioneered the new vaccine concept. "Our study demonstrates DoriVac's versatility and potential by taking a close look at the immune changes that are required to fight infectious viruses." Shih is also Professor at the Harvard Medical School and DFCI.
How DNA Origami Vaccines Are Built
In 2024, Shih's team at the Wyss Institute and Dana-Farber introduced DoriVac as a DNA nanotechnology-based vaccine platform with broad potential applications. Yang (Claire) Zeng, M.D., Ph.D., who led the effort with collaborators, showed that DoriVac can precisely present immune-stimulating adjuvant molecules to cells at the nanoscale.
Earlier studies in tumor-bearing mice demons