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

  1. Author:
    Wamhoff, Eike-Christian [ORCID]
    Knappe, Grant A
    Burds, Aurora A
    Du, Rebecca R
    Neun,Barry
    Difilippantonio,Simone
    Sanders,Chelsea
    Edmondson,Elijah
    Matta,Jennifer
    Dobrovolskaia,Marina
    Bathe, Mark [ORCID]

  2. Author Address

    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America., Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America., Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America., Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, United States of America., Laboratory of Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, United States of America., Molecular Histology and Pathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, United States of America.,
    1. Year: 2023
    2. Date: Apr 11
    3. Epub Date: 2023 04 11
  2. Journal: ACS Applied Bio Materials
  4. Type of Article: Article
  1. 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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External Sources

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  2. DOI: 10.1021/acsabm.3c00155
  3. PMID: 37040258

Library Notes

  1. Fiscal Year: FY2022-2023
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