Translating cancer research by synthetic biology

Shankar, Sumitra; Pillai, M. Radhakrishna

doi:10.1039/c1mb05016h

Cited by 15 publications

(13 citation statements)

References 64 publications

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“…Furthermore, they also helped to identify HSP promoters activated by different types of stress and the overload exerted in E. coli by the production of recombinant proteins. The HSP promoters can further have a significant role in another important field of synthetic biology, namely in engineering bacteria and viruses for therapeutic applications (Shankar and Pillai, 2011), like vaccines (Garmory et al, 2003) and gene delivery vectors (Drabner and Guzman, 2001). Besides sensing environmental pollution, it is feasible to program bacteria to sense the tumor environment and selectively release a drug to kill cancer cells (Anderson et al, 2006;Shankar and Pillai, 2011).…”

Section: Introductionmentioning

confidence: 99%

Selection of Escherichia coli heat shock promoters toward their application as stress probes

Rodrigues

Sousa

Prather

et al. 2014

Journal of Biotechnology

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Section: Introductionmentioning

confidence: 99%

Selection of Escherichia coli heat shock promoters toward their application as stress probes

Rodrigues

Sousa

Prather

et al. 2014

Journal of Biotechnology

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“…Synthetic biology therapy with multiple devices directed at cancer-specific gene pathways opens promising new avenues to improve cancer treatment [9]. On the basis of a detailed understanding of the genetic profiles of cancers, synthetic biologists try to produce predictable and robust biological devices with novel treatment functionalities that do not exist in nature.…”

Section: Introductionmentioning

confidence: 99%

Synthetic miRNA-Mowers Targeting miR-183-96-182 Cluster or miR-210 Inhibit Growth and Migration and Induce Apoptosis in Bladder Cancer Cells

et al. 2012

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BackgroundMicroRNAs (miRNAs) function as endogenous regulators of biological behaviors of human cancers. Several natural non-coding RNAs are reported to inhibit miRNAs by base-pairing interactions. These phenomena raise questions about the ability of artificial device to regulate miRNAs. The purpose of this study is to create synthetic devices that target a single miRNA or a miRNA cluster and to ascertain their therapeutic effects on the phenotypes of bladder cancer cells.Methodology/Principal FindingsTandem bulged miRNA binding sites were inserted into the 3′ untranslated region (UTR) of the SV-40 promoter-driven Renilla luciferase gene to construct two “miRNA-mowers” for suppression of miR-183-96-182 cluster or miR-210. A third device with tandem repeat sequences not complementary to any known miRNA was generated as an untargeted-control. In functional analyses, bladder cancer T24 and UM-UC-3 cells were transfected with each of the three devices, followed by assays for detection of their impacts. Luciferase assays indicated that the activities of the luciferase reporters in the miRNA-mowers were decreased to 30–50% of the untargeted-control. Using Real-Time qPCR, the expression levels of the target miRNAs were shown to be reduced 2-3-fold by the corresponding miRNA-mower. Cell growth, apoptosis, and migration were tested by MTT assay, flow cytometry assay, and in vitro scratch assay, respectively. Cell growth inhibition, increased apoptosis, and decreased motility were observed in miRNA-mowers-transfected bladder cancer cells.Conclusions/SignificanceNot only a single target miRNA but also the whole members of a target miRNA cluster can be blocked using this modular design strategy. Anti-cancer effects are induced by the synthetic miRNA-mowers in the bladder cancer cell lines. miR-183/96/182 cluster and miR-210 are shown to play oncogenic roles in bladder cancer. A potentially useful synthetic biology platform for miRNA loss-of-function study and cancer treatment has been established in this work.

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“…Shankar and Pillai [2011] discuss synthetic biology as an aid in effective and cheaper drug synthesis. A synthetic biological system could be designed to produce customized drugs for individual patient treatment.…”

Section: A Description Of the Genetic Priority Encoder Circuitmentioning

confidence: 99%

A Rule-Based Design Specification Language for Synthetic Biology

Oberortner

Bhatia

Lindgren

et al. 2014

J. Emerg. Technol. Comput. Syst.

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Synthetic Biology is an engineering discipline where parts of DNA sequences are composed into novel, complex systems that execute a desired biological function. Functioning and well-behaving biological systems adhere to a certain set of biological "rules". Data exchange standards and Bio-Design Automation (BDA) tools support the organization of part libraries and the exploration of rule-compliant compositions. In this work, we formally define a design specification language, enabling the integration of biological rules into the Synthetic Biology engineering process. The supported rules are divided into five categories: Counting, Pairing, Positioning, Orientation, and Interactions. We formally define the semantics of each rule, characterize the language's expressive power, and perform a case study in that we iteratively design a genetic Priority Encoder circuit following two alternative paradigms-rule-based and template-driven. Ultimately, we touch a method to approximate the complexity and time to computationally enumerate all rule-compliant designs. Our specification language may or may not be expressive enough to capture all designs that a Synthetic Biologist might want to describe, or the complexity one might find through experiments. However, computational support for the acquisition, specification, management, and application of biological rules is inevitable to understand the functioning of biology. ACM Reference Format:Ernst Oberortner, Swapnil Bhatia, Erik Lindgren, and Douglas Densmore. 2014. A rule-based design specification language for synthetic biology.

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Translating cancer research by synthetic biology

Cited by 15 publications

References 64 publications

Selection of Escherichia coli heat shock promoters toward their application as stress probes

Selection of Escherichia coli heat shock promoters toward their application as stress probes

Synthetic miRNA-Mowers Targeting miR-183-96-182 Cluster or miR-210 Inhibit Growth and Migration and Induce Apoptosis in Bladder Cancer Cells

A Rule-Based Design Specification Language for Synthetic Biology

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