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A research team led by Northwestern University nanomedicine expert Chad A. Mirkin and Sergei Gryaznov of AuraSense Therapeutics is the first to show spherical nucleic acids (SNAs) can be used as potent drugs to effectively train the immune system to fight disease, by either boosting or dampening the immune response. The initial treatment triggers a cell-specific immune response all over the body.
By increasing the body's immune response toward a specific cell type, SNAs could be used to target anything from influenza to different forms of cancer. They also can be used to suppress the immune response, a tactic important in treating autoimmune disorders, such as rheumatoid arthritis and psoriasis, where the body's immune system mistakenly attacks healthy tissues.
"The ability to selectively trigger the immune response with spherical nucleic acids presents a whole new way of thinking about drug development," said Mirkin, a corresponding author of the study. "Once developed fully, SNAs will lay the foundation for developing an entire new pipeline of drugs to treat a range of diseases, from psoriasis, lupus and rheumatoid arthritis to lymphoma, bladder cancer and prostate cancer."
Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering.
The study also shows that a spherical structure is the ideal architecture for delivering nucleic acids into cells for therapeutic purposes. The spherical arrangement of approximately 100 DNA strands attached to a benign nanoparticle core made of lipid or gold significantly outperformed nucleic acids in linear form.
The advantages of spherical nucleic acids in targeting the immune system include:
The study will be published the week of March 16 by the Proceedings of the National Academy of Sciences (PNAS).
Mirkin and his colleagues tested their SNAs head to head with known linear nucleic acids, targeting lymphoma and a form of autoimmune hepatitis. "The spherical nucleic acids always win from potency and speed standpoints, which corresponds with our understanding of their pathway of cellular entry," Mirkin said.
The researchers design SNAs for individual targets. Different DNA sequences are used to engage specific toll-like receptors, which result in either a stimulation or suppression of the immune response, depending on what the goal is.
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Spherical nucleic acids set stage for new paradigm in drug development