DoriVac DNA origami vaccine platform could rival mRNA technology, researchers say

A research team has engineered a vaccine delivery platform called DoriVac that uses DNA origami structures to present antigens to the immune system with a level of geometric precision that conventional vaccine formats cannot match. The platform arranges antigen molecules on a programmable DNA scaffold in specific spatial patterns, and initial animal studies show it generates strong immune responses that outperformed several comparison conditions, including equivalent antigen doses delivered without the DNA scaffold.

The reason this matters is structural. The immune system does not just detect the presence of foreign molecules. It also reads spatial information, including how closely antigens are spaced and how many are clustered together when they arrive at a lymph node. B cells, the immune cells that produce antibodies, are activated more efficiently when antigens are presented in regular, dense arrays that mimic the surface patterns found on actual pathogens. DoriVac is designed to exploit that biology by building the antigen array with nanometer-scale precision using folded DNA as the scaffold.

What DNA origami actually is and how DoriVac uses it

DNA origami is a technique, first demonstrated by Paul Rothemund at Caltech in 2006, in which a long single strand of DNA is folded into a defined two-dimensional or three-dimensional shape by mixing it with hundreds of short complementary DNA strands called staples. Each staple pulls a specific section of the long strand into a particular position, and the collective effect of all the staples determines the final shape. The structures self-assemble in solution and can be designed using software tools with atomic-level precision.

DoriVac uses a rectangular DNA origami tile, approximately 90 by 60 nanometers in size, as the presentation surface. Antigen molecules are attached to specific positions on the tile surface through covalent chemistry, allowing the researchers to control exactly how many antigens are displayed and at what spacing. In the published study, the team tested antigen spacings of 5, 10, and 20 nanometers and found that a 5 nanometer spacing produced the strongest B cell response, generating antibody titers approximately 8-fold higher than the same antigen presented without the scaffold at equivalent doses.

How DoriVac compares to mRNA vaccines

mRNA vaccines work by delivering genetic instructions to cells, which then produce the target antigen protein internally. The immune system detects the produced protein and builds a response. The process is indirect: the mRNA must enter cells, be translated into protein, and the protein must then be processed and presented on the cell surface before B cells and T cells can respond. The entire process depends on cellular machinery functioning correctly and on the mRNA surviving long enough in the body to be translated, which is why mRNA vaccines require lipid nanoparticle delivery systems and cold chain storage.

DoriVac takes a different approach. The antigen protein is produced separately, attached directly to the DNA scaffold outside of any cell, and the assembled structure is then injected. The immune system encounters a pre-formed antigen array rather than an instruction set it must execute first. This means the platform's performance is less dependent on cellular translation efficiency and more dependent on how well the DNA scaffold survives degradation in the body long enough to reach the lymph nodes where B cells reside.

The researchers addressed the stability problem by coating the DNA origami structure with a cationic polymer that protects it from nuclease degradation in biological fluids. Without coating, naked DNA origami degrades within minutes in serum. With the polymer coating used in the DoriVac study, the structures retained structural integrity for more than 24 hours in serum at 37 degrees Celsius, which is sufficient to allow lymph node trafficking after subcutaneous injection.

The immune response data from the mouse study

The published mouse study tested DoriVac carrying a model antigen, ovalbumin, alongside several comparison groups: free ovalbumin alone, ovalbumin mixed with a standard alum adjuvant, and ovalbumin attached to a random DNA scaffold without the precise geometric structure. DoriVac generated IgG antibody titers that were 8-fold higher than free ovalbumin and 3-fold higher than ovalbumin with alum adjuvant at week four post-immunization. The germinal center B cell response, which is the cellular process that drives antibody maturation and long-term immune memory, was also significantly elevated in the DoriVac group compared to all other conditions.

The comparison to alum is particularly relevant because alum is the adjuvant used in many licensed human vaccines, including hepatitis B and HPV vaccines. A platform that outperforms alum-adjuvanted antigen in generating germinal center responses has a meaningful performance benchmark to point to when justifying clinical development. The researchers note that DoriVac in the current form does not include a traditional adjuvant, and they expect performance to improve further when adjuvant molecules are co-attached to the scaffold in future iterations.

Cancer vaccine applications the team is targeting

The research team, based at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Dana-Farber Cancer Institute, is specifically interested in using DoriVac for cancer neoantigen vaccines. Neoantigens are mutant protein fragments that appear on cancer cells due to tumor-specific genetic mutations and are absent from healthy tissue. Each patient's tumor has a unique set of neoantigens, which means an effective cancer neoantigen vaccine must be personalized, manufactured quickly after tumor sequencing, and capable of activating both B cells and cytotoxic T cells that can directly kill tumor cells.

Moderna and BioNTech have both been running clinical trials for personalized mRNA neoantigen cancer vaccines. Moderna's mRNA-4157, in combination with pembrolizumab, showed in a Phase 2b trial published in 2023 that it reduced the risk of melanoma recurrence by 44 percent compared to pembrolizumab alone. DoriVac is still in preclinical stages, but the Harvard team's argument is that the structural control it provides over antigen presentation could generate broader and more durable T cell responses than current mRNA neoantigen approaches, particularly for cancers where the immune response to mRNA vaccines has been modest.

Manufacturing and scalability considerations

One practical question with any DNA-based platform is cost and scalability of manufacturing. DNA synthesis is more expensive per gram than mRNA synthesis, and the self-assembly process for DNA origami requires careful temperature control and purification steps to remove misfolded structures. The Wyss Institute team stated in the paper that their current synthesis protocol produces approximately 50 micrograms of assembled DoriVac structure per milliliter of reaction volume, with purification yields of around 70 percent. Scaling that to clinical production quantities would require investment in manufacturing process development comparable to what the mRNA vaccine field undertook between 2010 and 2020.

The paper was published in the journal Nature Nanotechnology in February 2026. The team has filed a provisional patent covering the DoriVac platform and antigen attachment chemistry, and they are in discussions with the National Cancer Institute's Cancer Moonshot program about funding a first-in-human Phase 1 trial targeting solid tumor neoantigens, which the team estimates could begin enrollment in late 2027 if preclinical safety studies complete on schedule.