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Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
Sijin Guo, Congcong Xu, Hongran Yin, Peixuan Guo, Jordan Hill, Fengmei Pi
Due to the lack of a universal nomenclature to categorize traditional therapeutic RNAs and RNA nanoparticles, the literatures on RNA immunogenicity have been controversial. Though the immunogenicity of traditional small RNAs has been widely investigated, there are only a limited number of studies focused on the immunogenicity of RNA nanoparticles. Recent studies revealed that pRNA-based RNA nanoparticles intrinsically display immunologically inert properties (Abdelmawla et al., 2011; Guo et al., 2017; Khisamutdinov et al., 2014a, 2014b; Shu et al., 2018). Specifically, no or negligible cytokine induction including TNF-α (Tumor Necrosis Factor-α), IL-6 (Interleukin-6) and IFN-α (Interferon-α) has been observed following treatment with pRNA nanoparticles in vitro and in vivo. TNF-α is a cytokine involved in systemic inflammation and the acute phase reaction. IL-6 is an interleukin secreted to stimulate immune responses during infection. IFN-α, which belongs to type I interferon, is also a cytokine involved in pro-inflammatory reactions released in response to the presence of viral pathogens. Besides, no stimulation of TLRs (Toll-like receptors) pathway, and no damage to normal tissue and organs was detected in multiple cell types and mice (Cui et al., 2015; Zhang et al., 2017). Similarly, RNA polygons (RNA triangle, square, and pentagon) constructed from the thermodynamically stable pRNA-3WJ were studied (Guo et al., 2017; Khisamutdinov et al., 2014a, 2014b). These RNA polygons have been considered nonimmunogenic and nontoxic because undetectable or negligible cytokine induction and cytotoxicity were observed in vitro and in vivo, compared to positive controls. Consistent results were found in three dimensional pRNA-based nanoparticles, including the RNA tetrahedron, RNA nanoprism, and RNA micelles (Guo et al., 2017; Khisamutdinov et al., 2016; Shu et al., 2018; Yin et al., 2018). Additionally, RNA aptamers, a family of RNA oligonucleotides commonly incorporated into RNA nanoparticles as targeted ligands to enhance binding specificity, have been reported to go unrecognized by the host immune system in various animal studies (Song, Lee, & Ban, 2012). These findings demonstrate that RNA nanoparticles equipped with targeting ligands can serve as safe delivery vectors in therapeutic interventions. Studies by Afonin Lab using a different system have also shown no immune response detection upon treatment with RNA nanoparticles in human peripheral blood mononuclear cells (PBMCs) from healthy donors (Hong et al., 2018). Interestingly, only complexation with a delivery carrier such as lipofectamine 2000 induced immunorecognition by PBMCs.
Evaluation of a single amino acid substitution at position 79 of human IFN-α2b in interferon-receptor assembly and activity
Published in Preparative Biochemistry and Biotechnology, 2019
Samira Talebi, Alireza Saeedinia, Mehdi Zeinoddini, Fathollah Ahmadpour, Majid Sadeghizadeh
Human interferon-α (IFN-α) is a member of the type I interferon (IFN-I) that are commonly recognized to prompt a potent innate immune response in contradiction of both cancers and viral infection.[18–20] IFN-α has been regularly used as an informing mediator for the treatment of several malignancies like renal cell cancer, hepatocellular carcinoma, and malignant melanoma by motivating of tumor cells apoptosis. Moreover, the effect of IFNα on cervical cancer has been studied by Shi et al. 2016.[21] HeLa cells were used as a testing model for the treatment of IFN-α on cervical cancer. The results show that IFNα prominently prevents the proliferation and prompts the HeLa cells apoptosis.
The effect of exposure to crude oil on the immune system. Health implications for people living near oil exploration activities
Published in International Journal of Environmental Health Research, 2021
Pauline McLoone, Olzhas Dyussupov, Zhaxybek Nurtlessov, Ussen Kenessariyev, Dinara Kenessary
Cytokine gene expression is altered in juvenile rockfish (Sebastes schlegeli) fed Iranian heavy crude oil (at 100 mg/kg) from the ‘Hebei Spirit’ oil spill in gelatin capsules (Kim et al. 2013). Interleukin-1β (IL-1β) and granulocyte colony-stimulating factor (G-CSF) mRNA expression in the liver were significantly higher in the oil-exposed group 12 h after exposure in comparison to control fish, but levels were reduced thereafter. As IL-1β and G-CSF stimulate neutrophils and over-activated neutrophils release superoxide that can cause cellular damage, it is possible that excessively induced IL-1β and G-CSF could account for the cell damage observed in some studies. Interferon-stimulated gene 15 (ISG15) expression was significantly down-regulated at 24 h post-exposure in the liver, spleen, and kidney of crude oil-exposed fish (200 mg/kg) in comparison to control fish tissues (Kim et al. 2013). The ISG15 protein has anti-viral activity and its expression is induced in response to Type I interferons (IFNs). Therefore, it was proposed that down-regulation of ISG15 could make the fish more vulnerable to viral infections. However, at 120 h post-exposure, liver and spleen ISG15 levels were significantly higher. Lee et al. (2018) fed rockfish Sebastes schlegeli gelatin capsulated weathered Iranian heavy crude oil containing 10, 100 or 200 mg oil/kg-body weight and found an increase in ISG15 mRNA expression levels in the 100-mg and 200-mg treated groups 6 h after exposure. The ISG15 mRNA expression levels subsequently declined 24 h after exposure. Furthermore, the highest expression levels of IL-1β, NFκB and p53 mRNA were observed in the 200 mg oil/kg-body weight treated fish 6 h after exposure. Levels then declined significantly within 24 h.