Wireframe
DNA origami can be used to fabricate virus-like particles for a range of biomedical applications, including the delivery of
nucleic acid therapeutics. However, the acute toxicity and biodistribution of these wireframe
nucleic acid nanoparticles (NANPs) have not previously been characterized in animal models. In the present study, we observed no indications of toxicity in BALB/c mice following therapeutically relevant dosage of unmodified
DNA-based NANPs via
intravenous administration, based on liver and kidney histology, liver biochemistry, and
body weight. Further, the immunotoxicity of these NANPs was minimal, as indicated by blood cell counts and
type-I interferon and pro-inflammatory
cytokines. In an SJL/J model of autoimmunity, we observed no indications of NANP-mediated
DNA-specific antibody response or immune-mediated kidney pathology following the intraperitoneal administration of NANPs. Finally, biodistribution studies revealed that these NANPs accumulate in the liver within one hour, concomitant with substantial renal clearance. Our observations support the continued development of wireframe
DNA-based NANPs as next-generation
nucleic acid therapeutic delivery platforms.