Evaluation of Nonmodified Wireframe DNA Origami for Acute Toxicity and Biodistribution in Mice

Abstract

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 been previously characterized in animal models. In the present study, we observed no indications of toxicity in BALB/c mice following a therapeutically relevant dosage of nonmodified DNA-based NANPs via intravenous administration, based on liver and kidney histology, liver and kidney 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.

DNA Nanostructure-Templated Antibody Complexes Provide Insights into the Geometric Requirements of Human Complement Cascade Activation

“…DNA nanostructures can be targeted to distinct cell types via binding motifs such as aptamers or directly displaying ligands for receptor binding and are stable in serum and in vivo (Figure ). , The use of DDT2–4 to induce in vivo dimerization, trimerization, or tetramerization of IgG, instead of hexamerization of Abs, would be a novel route to induce sublytic complement activation.…”

DNA nanostructure-templated antibody complexes provide insights into the geometric requirements of human complement cascade activation

“…DNA nanostructures can be targeted to distinct cell types via binding motifs such as aptamers 37 or directly displaying ligands for receptor binding, 38 and are stable in serum and in vivo ( Figure 4 ). 39, 40 The use of DDT2-4 to induce in vivo dimerization, trimerization or tetramerization of IgG, instead of hexamerization Abs, would be a novel route to induce sub-lytic complement activation.…”

DNA Nanostructures: Self‐Adjuvant Carriers for Highly Efficient Subunit Vaccines

“…Wamhoff et al characterized the acute toxicity and biodistribution of a wireframe DNA origami following intravenous and intraperitoneal administration, and found limited immunotoxicity and accumulation in the liver and kidney. [37] All of the aforementioned advantages make DNA nanostructures hold great potential to become outstanding self-adjuvant carriers for subunit vaccines.…”