Spherical nucleic acids

Came across an interesting article in Science highlighting the development of spherical nucleic acids (SNAs). A very cool video on YouTube explains it all.

Devised by the Dr Chad Mirkin’s group in Northwestern University in 1996, SNAs are composed of about a hundred strands of nucleic acids conjugated at their ends to a spherical nanoparticle core, usually made of gold, but in some instances can even be hollow. The key thing about SNAs is the ability for them to be taken up effectively by the cell without the need of cumbersome and sometimes toxic transfecting reagents. The particle is taken up by cell surface receptors into endosomes that prevent their contact with nucleases which normally degrade unprotected nucleic acid strands. Already several proof-in-concept studies have been done demonstrating their enhanced uptake. SNAs applied to the skin of mice were able to penetrate into skin cells to knockdown genes involved in psoriasis. They were also able to cross the blood-brain-barrier when injected into tail veins of mice, knocking down potential oncogenes and extending lifespan in a glioblastoma mouse model.

Mirkin is a renowned chemist specializing in nanotechnology and has founded several companies using SNAs. Nanosphere in Northbrook, Illinois, uses SNA’s additional ability to bind nucleic acids at low concentrations to detect the presence of microbes or pathogens in tissue samples. Aurasense Technologies now named Exicure, have attracted more than $27 million in funding and are using SNAs to stimulate an immonomodulatory response against cancer cells. The SNAs have sequences that resemble Toll-like receptor agonists and when administered in SNA form were noted to bring about an enhanced immunostimulatory response as compared to linear forms. They have already released positive preclinical data published in PNAS and their use in combination with checkpoint inhibitors are currently being explored in cancer treatment.

Northwestern University has recently received a $11.7 million grant from the US National Cancer Institute to apply this technology in the field of gene therapy and applications for this are proving to be wide-ranging. This has the potential to change how RNAi therapies are currently being administered, but it remains to be seen how well existing RNAi companies will take to this patented technology.


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