Mammalian synthetic circuits with RNA binding proteins for RNA-only delivery

Wróblewska, Liliana; Kitada, Tasuku; Endo, Kiyoshi; Siciliano, Velia; Stillo, Breanna; Saito, Hirohide; Weiss, Ron

doi:10.1038/nbt.3301

Cited by 184 publications

(218 citation statements)

References 26 publications

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“…Although L7Ae:K-turn has been exploited to build regulatory switches and circuits (27–30,32,33), most previous studies demonstrate the conceptual design in model cancer cell lines (e.g. HeLa) and have yet to apply L7Ae:K-turn system to aggressive tumorigenic cancer cells (e.g.…”

Section: Discussionmentioning

confidence: 99%

Synthetic switch-based baculovirus for transgene expression control and selective killing of hepatocellular carcinoma cells

Lin

Tseng

Shen

et al. 2018

Nucleic Acids Research

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Baculovirus (BV) holds promise as a vector for anticancer gene delivery to combat the most common liver cancer–hepatocellular carcinoma (HCC). However, in vivo BV administration inevitably results in BV entry into non-HCC normal cells, leaky anticancer gene expression and possible toxicity. To improve the safety, we employed synthetic biology to engineer BV for transgene expression regulation. We first uncovered that miR-196a and miR-126 are exclusively expressed in HCC and normal cells, respectively, which allowed us to engineer a sensor based on distinct miRNA expression signature. We next assembled a synthetic switch by coupling the miRNA sensor and RNA binding protein L7Ae for translational repression, and incorporated the entire device into a single BV. The recombinant BV efficiently entered HCC and normal cells and enabled cis-acting transgene expression control, by turning OFF transgene expression in normal cells while switching ON transgene expression in HCC cells. Using pro-apoptotic hBax as the transgene, the switch-based BV selectively killed HCC cells in separate culture and mixed culture of HCC and normal cells. These data demonstrate the potential of synthetic switch-based BV to distinguish HCC and non-HCC normal cells for selective transgene expression control and killing of HCC cells.

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Section: Discussionmentioning

confidence: 99%

Synthetic switch-based baculovirus for transgene expression control and selective killing of hepatocellular carcinoma cells

Lin

Tseng

Shen

et al. 2018

Nucleic Acids Research

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“…Extra-genomic artificial chromosomes are emerging vectors that are maintained at a single copy, replicate during mitosis, and carry payloads of up to many megabases [41]. Finally, plasmid transfection, RNA replicons [42], and non-integrating viral vectors are transient delivery options. Each method confers a unique profile of variation in gene expression and risk of gene silencing, and how such variation can impact device characterization and performance is a topic of ongoing investigation.…”

Section: Principles For Engineering Cell-based Therapiesmentioning

confidence: 99%

Building with intent: Technologies and principles for engineering mammalian cell-based therapies to sense and respond

Muldoon

Donahue

Dolberg

et al. 2017

Current Opinion in Biomedical Engineering

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The engineering of cells as programmable devices has enabled therapeutic strategies that could not otherwise be achieved. Such strategies include recapitulating and enhancing native cellular functions and composing novel functions. These novel functions may be composed using both natural and engineered biological components, with the latter exemplified by the development of synthetic receptor and signal transduction systems. Recent advances in implementing these approaches include the treatment of cancer, where the most clinical progress has been made to date, and the treatment of diabetes. Principles for engineering cell-based therapies that are safe and effective are increasingly needed and beginning to emerge, and will be essential in the development of this new class of therapeutics.

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“…Refinement of the cell classifiers using RNA replicons and RNA-binding proteins provides an even more robust and finely tuneable system (102) Another complex device with therapeutic potential consists of sender and receiver cells, contained in alginate-poly-L-lysine-alginate capsules, circulating as prosthetic delivery units in the mouse bloodstream, and responding to an acetaldehyde signal (103). These units form multicellular networks, which behave as hormone-like information-processing devices: exogenous signals trigger Widespread genome editing will transform therapeutics and genetics, likely leading to the greatest insights of all into the relationship between genotype, phenotype, and the functioning of cells.…”

Section: Multicellular Mammalian Synthetic Network and Synthetic Thementioning

confidence: 99%

“…Already, mammalian synthetic biology has provided circuits oriented toward therapeutics. RNA-based multi-input Boolean logic cell classifiers can specifically recognize and kill cancer-derived HeLa cells, rather than HEK293 and MCF7 cells, according to their miRNA expression patterns (101,102).…”

Section: Multicellular Mammalian Synthetic Network and Synthetic Thementioning

confidence: 99%

From noise to synthetic nucleoli: can synthetic biology achieve new insights?

Ciechonska

Grob

Isalan

2016

Integrative Biology

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Synthetic biology involves the engineering of life either to construct functional biological devices or to test the functioning of biological systems, thus achieving countless insights into the inner workings of the cells. Here, we provide an overview of the impact that the field of synthetic biology has had in the areas of gene expression, cell heterogeneity (noise), coupling of growth and energy usage to expression, and spatiotemporal dynamics of cellular machinery. We compare bacterial and mammalian systems, which currently provide some of the most-developed engineering frameworks. Over the last decade, the many insights that have arisen from synthetic biology have triggered an exciting transition from "creating in order to understand" towards "creating in order to cure." Abstract (141 words)Synthetic biology aims to re-organise and control biological components to make functional devices. Along the way, the iterative process of designing and testing gene circuits has the potential to yield many insights into the functioning of the underlying chassis of cells. Thus, synthetic biology is converging with disciplines such as systems biology and even classical cell biology, to give a new level of predictability to gene expression, cell metabolism and cellular signalling networks.This review gives an overview of the contributions that synthetic biology has made in understanding gene expression, in terms of cell heterogeneity (noise), the coupling of growth and energy usage to expression, and spatiotemporal considerations. We mainly compare progress in bacterial and mammalian systems, which have some of the most-developed engineering frameworks.Overall, one view of synthetic biology can be neatly summarised as "creating in order to understand."

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Mammalian synthetic circuits with RNA binding proteins for RNA-only delivery

Cited by 184 publications

References 26 publications

Synthetic switch-based baculovirus for transgene expression control and selective killing of hepatocellular carcinoma cells

Synthetic switch-based baculovirus for transgene expression control and selective killing of hepatocellular carcinoma cells

Building with intent: Technologies and principles for engineering mammalian cell-based therapies to sense and respond

From noise to synthetic nucleoli: can synthetic biology achieve new insights?

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