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荧光标记痘苗病毒基因组可实现对溶瘤潜力的快速高效测定及溶瘤调节剂的发现。

Fluorescent Tagged Vaccinia Virus Genome Allows Rapid and Efficient Measurement of Oncolytic Potential and Discovery of Oncolytic Modulators.

作者信息

Gallardo Franck, Schmitt Doris, Brandely Renée, Brua Catherine, Silvestre Nathalie, Findeli Annie, Foloppe Johann, Top Sokunthea, Kappler-Gratias Sandrine, Quentin-Froignant Charlotte, Morin Renaud, Lagarde Jean-Michel, Bystricky Kerstin, Bertagnoli Stéphane, Erbs Philippe

机构信息

NeoVirTech SAS, 31106 Toulouse, France.

Transgene SA, 67405 Illkirch-Graffenstaden, France.

出版信息

Biomedicines. 2020 Nov 26;8(12):543. doi: 10.3390/biomedicines8120543.

DOI:10.3390/biomedicines8120543
PMID:33256205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7760631/
Abstract

As a live biologic agent, oncolytic vaccinia virus has the ability to target and selectively amplify at tumor sites. We have previously reported that deletion of thymidine kinase and ribonucleotide reductase genes in vaccinia virus can increase the safety and efficacy of the virus. Here, to allow direct visualization of the viral genome in living cells, we incorporated the ANCH target sequence and the OR3-Santaka gene in the double-deleted vaccinia virus. Infection of human tumor cells with ANCHOR3-tagged vaccinia virus enables visualization and quantification of viral genome dynamics in living cells. The results show that the ANCHOR technology permits the measurement of the oncolytic potential of the double deleted vaccinia virus. Quantitative analysis of infection kinetics and of viral DNA replication allow rapid and efficient identification of inhibitors and activators of oncolytic activity. Our results highlight the potential application of the ANCHOR technology to track vaccinia virus and virtually any kind of poxvirus in living cells.

摘要

作为一种活生物制剂，溶瘤痘苗病毒能够在肿瘤部位靶向并选择性扩增。我们之前报道过，痘苗病毒中胸苷激酶和核糖核苷酸还原酶基因的缺失可提高病毒的安全性和有效性。在此，为了在活细胞中直接观察病毒基因组，我们在双缺失痘苗病毒中整合了ANCH靶序列和OR3-Santaka基因。用ANCHOR3标记的痘苗病毒感染人肿瘤细胞能够在活细胞中观察和定量病毒基因组动态。结果表明，ANCHOR技术可用于测量双缺失痘苗病毒的溶瘤潜力。对感染动力学和病毒DNA复制进行定量分析，能够快速有效地鉴定溶瘤活性的抑制剂和激活剂。我们的结果突出了ANCHOR技术在活细胞中追踪痘苗病毒以及几乎任何一种痘病毒的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/9d284538ed1e/biomedicines-08-00543-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/19074d1d090e/biomedicines-08-00543-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/3d6d05654a2e/biomedicines-08-00543-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/89a43a0ea5fa/biomedicines-08-00543-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/7fd5804cbbec/biomedicines-08-00543-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/c3070d81e277/biomedicines-08-00543-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/9d284538ed1e/biomedicines-08-00543-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/19074d1d090e/biomedicines-08-00543-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/3d6d05654a2e/biomedicines-08-00543-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/89a43a0ea5fa/biomedicines-08-00543-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/7fd5804cbbec/biomedicines-08-00543-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/c3070d81e277/biomedicines-08-00543-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a54/7760631/9d284538ed1e/biomedicines-08-00543-g006.jpg

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