A Recombinant Vaccinia Virus Expressing a Sodium/Iodide Symporter for Theranostics of Malignant Tumors Using Synchrotron Radiation

IF 1 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
A. V. Semenova, A. A. Grazhdantseva, G. F. Sivolobova, G. A. Kudrov, A. S. Kabanov, A. A. Legkodymov, K. E. Kuper, A. P. Agafonov, G. V. Kochneva
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Abstract

A recombinant strain of the vaccinia virus, VV-mNIS-dGF, has been constructed. The genome of this strain contains an insertion of the mouse sodium/iodide symporter transgene (mNIS). This insertion is located in the deleted region of the viral thymidine kinase gene (tk). In addition, the viral growth factor gene (vgf) was deleted, ensuring that the virus had an attenuated effect on normal cells without affecting its replication in cancer ones. The antitumor activity of the VV-mNIS-dGF strain in two mouse cancer models, melanoma B16-F10 and colorectal carcinoma CT-26, was studied. In both models, the strain exhibited high oncolytic activity, efficiently expressed the mNIS and accumulated iodide in tumor cells in both in vitro experiments and in vivo on mouse allografts. Quantification of the iodide content in tumors was performed by elemental analysis using X-ray Fluorescence Analysis with Synchrotron Radiation (XRF-SR). The results indicate the possibility of using the VV-mNIS-dGF strain for both therapy and diagnosis (theranostics) of malignant tumors.

Abstract Image

表达钠/碘同体的重组痘苗病毒在同步辐射治疗恶性肿瘤中的应用
构建了牛痘病毒重组株VV-mNIS-dGF。该菌株的基因组包含一个插入的小鼠钠/碘同体转基因(mNIS)。该插入位于病毒胸苷激酶基因(tk)的缺失区域。此外,病毒生长因子基因(vgf)被删除,确保病毒对正常细胞的作用减弱,而不影响其在癌症细胞中的复制。研究了VV-mNIS-dGF菌株在黑色素瘤B16-F10和结直肠癌CT-26两种小鼠肿瘤模型中的抗肿瘤活性。在这两种模型中,菌株在体外和体内对小鼠同种异体移植物均表现出高的溶瘤活性,高效表达mNIS和肿瘤细胞中积累的碘化物。采用同步辐射x射线荧光分析(XRF-SR)进行元素分析,定量测定肿瘤中碘的含量。结果表明,利用VV-mNIS-dGF菌株进行恶性肿瘤的治疗和诊断(治疗学)的可能性。
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来源期刊
Applied Biochemistry and Microbiology
Applied Biochemistry and Microbiology 生物-生物工程与应用微生物
CiteScore
1.70
自引率
12.50%
发文量
75
审稿时长
6-12 weeks
期刊介绍: Applied Biochemistry and Microbiology is an international peer reviewed journal that publishes original articles on biochemistry and microbiology that have or may have practical applications. The studies include: enzymes and mechanisms of enzymatic reactions, biosynthesis of low and high molecular physiologically active compounds; the studies of their structure and properties; biogenesis and pathways of their regulation; metabolism of producers of biologically active compounds, biocatalysis in organic synthesis, applied genetics of microorganisms, applied enzymology; protein and metabolic engineering, biochemical bases of phytoimmunity, applied aspects of biochemical and immunochemical analysis; biodegradation of xenobiotics; biosensors; biomedical research (without clinical studies). Along with experimental works, the journal publishes descriptions of novel research techniques and reviews on selected topics.
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