Evaluation of Nonmodified Wireframe DNA Origami for Acute Toxicity and Biodistribution in Mice.
ACS Appl Bio Mater
; 6(5): 1960-1969, 2023 05 15.
Article
en En
| MEDLINE
| ID: mdl-37040258
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.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ácidos Nucleicos
/
Nanopartículas
Límite:
Animals
Idioma:
En
Revista:
ACS Appl Bio Mater
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos