Harvard's DNA Origami Vaccine Matches mRNA Shots in Immune Response While Eliminating Cold Chain Requirements
Harvard's DoriVac platform, built from self-assembling DNA nanostructures, matches mRNA vaccine immune responses while eliminating cold chain requirements, a Nature Biomedical Engineering study shows.
Overview
A vaccine platform built from folded DNA nanostructures has matched the immune responses generated by leading mRNA vaccines while eliminating the cold chain storage requirements that have limited global distribution, according to a study published in Nature Biomedical Engineering on March 11, 2026. The platform, called DoriVac, was developed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University in collaboration with the Dana-Farber Cancer Institute.
In head-to-head comparisons with Moderna and Pfizer-BioNTech mRNA vaccines delivered through lipid nanoparticles, DoriVac vaccines targeting SARS-CoV-2 produced comparable antibody-driven and T cell-driven immune activation in both mouse studies and human lymph node-on-a-chip models. The researchers also designed DoriVac vaccines targeting conserved spike protein regions of HIV and Ebola, with all three formulations generating strong humoral and cellular immunity.
How DNA Origami Becomes a Vaccine
DoriVac exploits a technique known as DNA origami, in which long strands of DNA are programmed to fold into precise three-dimensional shapes at the nanoscale. The resulting structures are tiny, self-assembling square nanoparticles with two functional faces: one side displays adjuvant molecules — immune-stimulating compounds — arranged at precisely controlled nanometer distances, while the opposite side presents selected antigens such as peptides or proteins from the target pathogen.
This spatial precision is what distinguishes DoriVac from conventional vaccine platforms. By controlling the exact spacing between adjuvant molecules, the researchers can tune how strongly dendritic cells — the immune system’s sentinels — are activated upon encountering the nanoparticle. William Shih, a Wyss Institute Core Faculty member and co-corresponding author of the study, stated that “with the DoriVac platform, we have developed an extremely flexible chassis with unprecedented control over vaccine composition,” according to the Wyss Institute announcement.
The study focused on HR2 peptides, which are conserved regions of spike proteins shared across multiple virus families. By targeting these stable regions rather than rapidly mutating surface features, the researchers aimed to develop vaccines with broader and more durable protection.
Results in Animal and Human Models
In mouse studies, DoriVac vaccines targeting SARS-CoV-2 triggered strong immune responses encompassing both antibody production and T cell activation. The nanostructured vaccines generated significantly greater activation of dendritic cells, B cells, and memory and cytotoxic T cells compared to the same vaccine components delivered without the DNA origami scaffold.
The researchers then tested the platform using human lymph node-on-a-chip technology — an engineered tissue model that replicates the architecture and immune cell populations of a human lymph node. In these models, DoriVac activated human dendritic cells and significantly increased their production of inflammatory cytokines. The platform also increased populations of both CD4+ helper T cells and CD8+ cytotoxic T cells, the two arms of the adaptive immune response most critical for clearing viral infections.
When compared directly with commercial mRNA-lipid nanoparticle vaccines from Moderna and Pfizer-BioNTech, DoriVac produced similarly strong anti-viral immune responses in the human models while demonstrating advantages in stability and manufacturability.
Manufacturing and Distribution Advantages
The practical implications of DoriVac extend beyond immunological performance. mRNA vaccines require storage at ultra-cold temperatures — typically minus 20 to minus 80 degrees Celsius — and rely on lipid nanoparticle formulations that present significant manufacturing complexity. These requirements contributed to inequitable global distribution during the COVID-19 pandemic, with many low- and middle-income countries unable to maintain the cold chain infrastructure needed to deploy mRNA vaccines effectively.
DoriVac vaccines do not require the same cold chain infrastructure, according to the researchers. The DNA origami nanostructures are inherently more stable than mRNA-lipid nanoparticle formulations and can be manufactured through a simpler process with better control over composition. The Wyss Institute researchers noted that these properties could enable more effective distribution in under-resourced regions and overcome some of the manufacturing complexities that have constrained mRNA vaccine production.
Research Team and Next Steps
The study was led by Yang Claire Zeng, who serves as first and co-corresponding author and is CEO and CTO of DoriNano, a company formed to commercialize the DoriVac platform. Co-corresponding authors include Shih and Donald Ingber, the Wyss Institute’s founding director. Additional co-first and corresponding authors include Olivia Young, Longlong Si, Min Wen Ku, and Girija Goyal.
The research was funded by the Wyss Institute Director’s Fund, the National Institutes of Health, the Bill and Melinda Gates Foundation, and other sources. The team has previously demonstrated DoriVac’s potential in cancer immunotherapy applications, and the new infectious disease results expand the platform’s demonstrated range.
While DoriVac remains in preclinical development, the combination of matched immunological performance, room-temperature stability, and simplified manufacturing positions the platform as a potential successor technology to mRNA vaccines — particularly for applications where cold chain logistics present barriers to equitable global access.