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. 2019 Oct 22;10:4801. doi: 10.1038/s41467-019-12794-2

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Programmable oncolytic adenovirus by using sensory switch circuit. a The schematic diagram of synthetic oncolytic adenovirus. A sensory switch circuit with mutual inhibitions controls the expression of adenoviral E1A gene and immune effector by sensing one promoter and two microRNA inputs, resulting in selective viral replication in cancer cells and modulations of immune responses. pCancer cancer-specific promoter, miR-a a microRNA expresses at a high level in normal cells but at a low level in cancer cells, miR-b a cancer-specific microRNA. The sensory switch circuit produces high levels of E1A and immune effector when the following three conditions are satisfied: pCancer is activated, miR-a is low and miR-b is high. b The schematic diagram of sensory switch circuit is shown in the left. A sensory switch circuit consists of a Gal4VP16 activator gene driven by pCancer, and two mutually inhibiting repressor genes controlled by two miRNAs respectively. UAS upstream activation sites, Effector immune effector, L self-cleavage 2A linker, Ta and Tb binding sites of two repressors (Rep-a and Rep-b) respectively