Genotoxicity evaluation of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG), a novel siRNA nanoparticle for the treatment of fibrotic disease

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Title
Genotoxicity evaluation of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG), a novel siRNA nanoparticle for the treatment of fibrotic disease
Author(s)
H Y Kim; T R Kim; S H Kim; I H Kim; Y Ko; S Yun; In Chul Lee; H O Park; J C Kim
Bibliographic Citation
Drug and Chemical Toxicology, vol. 45, no. 5, pp. 2109-2115
Publication Year
2022
Abstract
The self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) is a novel small-interfering RNA (siRNA) nanoparticle that is used for treatment of pulmonary fibrosis. We investigated the potential genotoxicity of SAMiRNA-AREG based on the guidelines published by the Organization for Economic Cooperation and Development. In the bacterial reverse mutation assay (Ames test), SAMiRNA-AREG did not induce mutations in Salmonella typhimurium TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2uvrA at concentrations of up to 3000 μg/plate with or without metabolic activation. The SAMiRNA-AREG (concentrations up to 500 μg/mL) did not induce chromosomal aberrations in cultured Chinese hamster lung cells with or without metabolic activation. In the in vivo mouse bone marrow micronucleus assay, the SAMiRNA-AREG (concentrations up to 300 mg/kg body weight) did not affect the proportions of polychromatic erythrocytes and total erythrocytes, nor did it increase the number of micronucleated polychromatic erythrocytes in ICR mice. Collectively, these results suggest that SAMiRNA-AREG is safe with regard to genotoxicity such as mutagenesis or clastogenesis under the present experimental conditions. These results might support the safety of SAMiRNA-AREG as a potential therapeutic agent for pharmaceutical development.
Keyword
Self-assembled-micelle interfering RNANanoparticleGenotoxicitySafety evaluationAmphiregulinGLP study
ISSN
0148-0545
Publisher
T&F (Taylor & Francis)
DOI
http://dx.doi.org/10.1080/01480545.2021.1908003
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
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