Back

Evaluation of non-modified wireframe DNA origami for acute toxicity and biodistribution in mice

Wamhoff, E.-C.; Knappe, G. A.; Burds, A. A.; Du, R. R.; Neun, B.; Difilippantonio, S.; Sanders, C.; Edmondson, E.; Matta, J. L.; Dobrovolskaia, M.; Bathe, M.

2023-02-27 pharmacology and toxicology
10.1101/2023.02.25.530026 bioRxiv
Show 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 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.

Matching journals

The top 6 journals account for 50% of the predicted probability mass.

1
ACS Nano
● 113 papers in training set
Top 0.1%
16.3%
Similar papers in this journal
2
Small
○ 78 papers in training set
Top 0.1%
11.8%
Similar papers in this journal
3
Journal of Controlled Release
○ 44 papers in training set
Top 0.1%
9.7%
Similar papers in this journal
4
Journal of Nanobiotechnology
○ 14 papers in training set
Top 0.1%
6.2%
Similar papers in this journal
5
Nature Communications
○ 5641 papers in training set
Top 27%
5.4%
Similar papers in this journal
6
Scientific Reports
○ 3612 papers in training set
Top 32%
3.2%
50% of probability mass above
7
Nanoscale Advances
● 15 papers in training set
Top 0.1%
3.2%
8
Advanced Healthcare Materials
○ 85 papers in training set
Top 0.7%
2.8%
9
Biomaterials Science
● 24 papers in training set
Top 0.2%
2.6%
10
Molecular Therapy Nucleic Acids
○ 39 papers in training set
Top 0.3%
2.4%
11
ACS Central Science
● 71 papers in training set
Top 0.5%
2.4%
12
Advanced Science
○ 286 papers in training set
Top 3%
2.4%
13
Advanced Functional Materials
○ 46 papers in training set
Top 0.6%
2.1%
14
ACS Biomaterials Science & Engineering
● 37 papers in training set
Top 0.5%
1.7%
15
Angewandte Chemie International Edition
○ 93 papers in training set
Top 1%
1.5%
16
Bioconjugate Chemistry
● 20 papers in training set
Top 0.2%
1.4%
17
Lab Animal
○ 11 papers in training set
Top 0.1%
1.3%
18
Biomaterials
○ 84 papers in training set
Top 1%
1.1%
19
Chemical Research in Toxicology
● 10 papers in training set
Top 0.2%
1.1%
20
Nanoscale
● 42 papers in training set
Top 0.6%
1.1%
21
Advanced Therapeutics
○ 17 papers in training set
Top 0.2%
1.1%
22
Journal of the American Chemical Society
● 217 papers in training set
Top 2%
1.0%
23
Environmental Science & Technology
● 64 papers in training set
Top 1.0%
1.0%
24
Molecular Therapy
○ 81 papers in training set
Top 2%
0.8%
25
Journal of Extracellular Biology
○ 22 papers in training set
Top 0.2%
0.8%
26
Nature Biotechnology
○ 172 papers in training set
Top 5%
0.6%
27
Small Methods
○ 29 papers in training set
Top 0.9%
0.6%
28
Journal of Hazardous Materials
○ 21 papers in training set
Top 0.5%
0.6%
29
Nature Nanotechnology
○ 32 papers in training set
Top 0.7%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.