ISD45 spherical nucleic acids

ISD45 spherical nucleic acids (ISD45-SNAs) are an experimental nanomedicine modality consisting of a gold nanoparticle core functionalized with a dense shell of interferon-stimulatory DNA (ISD45) oligonucleotides. Designed for the treatment of glioblastoma (GBM), these structures act as potent agonists of cyclic GMP-AMP synthase (cGAS), the primary cytosolic sensor of double-stranded DNA. By binding to cGAS, ISD45-SNAs trigger the catalytic production of endogenous cyclic dinucleotides, which subsequently activate the STING (Stimulator of Interferon Genes) pathway. This mechanism reprograms the immunosuppressive tumor microenvironment into a proinflammatory state, characterized by an enrichment of effector T cells and proinflammatory macrophages. Preclinical studies demonstrate that ISD45-SNAs, administered intranasally or intratumorally, inhibit tumor growth more effectively than synthetic cyclic dinucleotides and can induce long-term antiglioma immunity, particularly when co-administered with immune checkpoint inhibitors.

Other names

ISD45-SNAISD-45-SNAISD 45-SNAcGAS-activating spherical nucleic acidscGAS-agonistic spherical nucleic acids