Researchers from the Institute of Biomedical Engineering (BME) at the University of Toronto have developed a new method to precisely control the structure and function of immune complexes (ICs) using DNA origami. The findings, published in a recent issue of ACS Nano, could advance our understanding of immune system responses and pave the way for improved vaccines and immunotherapies.
Immune complex formation is a critical process in the body’s defense, occurring when antibodies bind foreign antigens, marking them for destruction by the immune system. The immune responses triggered by immune complexes depend on their physical properties, such as size and composition. However, traditional methods for synthesizing ICs produce heterogeneous assemblies, limiting the ability to predict or control these responses.
A cornerstone in Professor Leo Chou’s research is DNA origami, which uses DNA––the same biological building block that makes up the genome–– to create nano-sized structures onto which molecules can be positioned with nanometer precision.
The research team designed DNA nanostructures decorated with antigens and studied their interactions with antibodies. By tuning factors such as antigen spacing and valency on the nanoparticle, the researchers discovered that the spatial pattern of antigens controlled the formation of immune complexes as either single monomers or large aggregates. This could significantly change how these structures interact with immune cells and elicit downstream immune responses.
“We were surprised that a difference of just a few nanometers in antigen spacing had such a drastic effect on immune complex structure. This could have implications for vaccine and immunotherapy design,” explains Professor Leo Chou, the corresponding author of the study. ” DNA origami provided us with the perfect tool to tackle this question.”
Using DNA origami, the researchers were able to design a library of synthetic immune complexes or various configurations, and test their uptake by immune cells, such as macrophages and dendritic cells. The experiments demonstrated that IC structure directly influenced how these cells engaged and internalized the complexes.
“By engineering the structure of immune complexes using DNA origami, we were able to systematically explore how IC design impacts their interactions with immune cells,” says Travis Douglas, a PhD student and the study’s lead author. “These synthetic immune complexes are quite versatile and can be programmed with different functionalities. We are excited to explore their utility such as delivery systems for immunotherapies and vaccines.”
Looking ahead, the team plans to expand their research by studying how these synthetic ICs can be formed from different types of antibodies as well as how they behave in vivo. ” This is only the beginning of this project. We’ve created immune complexes that do not exist in Nature. We need to better characterize their immune responses both in vitro and in vivo,” says Chou. “We believe DNA nanotechnology offers an exciting opportunity to create programmable immune interventions.”