Xiaowei Liu examines cells to test whether DNA nanostructures could reside comfortably within the appropriate compartment of the cells and be stable for several hours – long enough to set in motion an immune cascade
Scientists at the Biodesign Institute at Arizona State University have turned to DNA nanotechnology to make an entirely new class of synthetic vaccines. In a study published in the journal Nano Letters, Biodesign immunologist Yung Chang joined forces with her colleagues, including DNA nanotechnology innovator Hao Yan, to develop the first vaccine complex that could be delivered safely and effectively by piggybacking onto self-assembled, three-dimensional DNA nanostructures.
‘When Hao treated DNA not as a genetic material, but as a scaffolding material, that made me think of possible applications in immunology,’ said Chang, an associate professor in the School of Life Sciences and a researcher in the Biodesign Institute’s Center for Infectious Diseases and Vaccinology. ‘This provided a great opportunity to try to use these DNA scaffolds to make a synthetic vaccine. We wanted to mimic the assembly of molecules that can trigger a safe and powerful immune response in the body.’
DNA nanotechnology has an advantage of being a programmable system that can precisely organise molecules to mimic the actions of natural molecules in the body. The researchers wanted to test several different sizes and shapes of DNA nanostructures and attach molecules to them to see if they could trigger an immune response. With their biomimicry approach, the vaccine complexes they tested closely resembled natural viral particles in size and shape.
As proof of concept, they tethered onto separate pyramid-shaped and branched DNA structures a model immune stimulating protein called streptavidin (STV) and an immune response boosting adjuvant (CpG oligo-deoxynucletides) to make their synthetic vaccine complexes.
First, the group had to prove that the target cells could gobble the nanostructures up. By attaching a light-emitting tracer molecule to the nanostructures, they found the nanostructures residing comfortably within the appropriate compartment of the cells and stable for several hours – long enough to set in motion an immune cascade.
Next, in a mouse challenge, they targeted the delivery of their vaccine cargo to cells that are first responders in initiating an effective immune response, co-ordinating interaction of important components, such as: antigen presenting cells, including macrophages, dendritic cells and B cells. To properly test all variables, they injected: the full vaccine complex; STV (antigen) alone; and the CpG mixed with STV.
Over the course of 70 days, the group found that mice immunised with the full vaccine complex developed an immune response up to 9-fold higher than the CpG mixed with STV. The pyramid (tetrahedral) shaped structure generated the greatest immune response. Not only was immune response to the vaccine complex specific and effective, but also safe: no immune response triggered from introducing the DNA platform alone.
With the ability to target specific immune cells to generate a response, the team envisions applications where they could develop vaccines that require multiple components, or customise their targets to tailor the immune response. Furthermore, there is the potential to develop targeted therapeutics in a similar manner as some of the new generation of cancer drugs.