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  • 1
    Online Resource
    Online Resource
    Light‐Controlled Mammalian Cells and Their Therapeutic Applications in Synthetic Biology
    Wiley ; 2019
    In:  Advanced Science Vol. 6, No. 1 ( 2019-01)
    Details
    In: Advanced Science, Wiley, Vol. 6, No. 1 ( 2019-01)
    Abstract: The ability to remote control the expression of therapeutic genes in mammalian cells in order to treat disease is a central goal of synthetic biology‐inspired therapeutic strategies. Furthermore, optogenetics, a combination of light and genetic sciences, provides an unprecedented ability to use light for precise control of various cellular activities with high spatiotemporal resolution. Recent work to combine optogenetics and therapeutic synthetic biology has led to the engineering of light‐controllable designer cells, whose behavior can be regulated precisely and noninvasively. This Review focuses mainly on non‐neural optogenetic systems, which are often used in synthetic biology, and their applications in genetic programing of mammalian cells. Here, a brief overview of the optogenetic tool kit that is available to build light‐sensitive mammalian cells is provided. Then, recently developed strategies for the control of designer cells with specific biological functions are summarized. Recent translational applications of optogenetically engineered cells are also highlighted, ranging from in vitro basic research to in vivo light‐controlled gene therapy. Finally, current bottlenecks, possible solutions, and future prospects for optogenetics in synthetic biology are discussed.
    Type of Medium: Online Resource
    ISSN: 2198-3844 , 2198-3844
    URL: Issue
    URL: Article
    DOI: 10.1002/advs.v6.1
    DOI: 10.1002/advs.201800952
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2808093-2
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  • 2
    Online Resource
    Online Resource
    Synthetic biology-based optogenetic approaches to control therapeutic designer cells
    Elsevier BV ; 2021
    In:  Current Opinion in Systems Biology Vol. 28 ( 2021-12), p. 100396-
    Details
    In: Current Opinion in Systems Biology, Elsevier BV, Vol. 28 ( 2021-12), p. 100396-
    Type of Medium: Online Resource
    ISSN: 2452-3100
    URL: Article
    DOI: 10.1016/j.coisb.2021.100396
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2879721-8
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  • 3
    Online Resource
    Online Resource
    Therapeutic cell engineering: designing programmable synthetic genetic circuits in mammalian cells
    Oxford University Press (OUP) ; 2022
    In:  Protein & Cell Vol. 13, No. 7 ( 2022-07), p. 476-489
    Details
    In: Protein & Cell, Oxford University Press (OUP), Vol. 13, No. 7 ( 2022-07), p. 476-489
    Abstract: Cell therapy approaches that employ engineered mammalian cells for on-demand production of therapeutic agents in the patient’s body are moving beyond proof-of-concept in translational medicine. The therapeutic cells can be customized to sense user-defined signals, process them, and respond in a programmable and predictable way. In this paper, we introduce the available tools and strategies employed to design therapeutic cells. Then, various approaches to control cell behaviors, including open-loop and closed-loop systems, are discussed. We also highlight therapeutic applications of engineered cells for early diagnosis and treatment of various diseases in the clinic and in experimental disease models. Finally, we consider emerging technologies such as digital devices and their potential for incorporation into future cell-based therapies.
    Type of Medium: Online Resource
    ISSN: 1674-8018
    URL: Article
    DOI: 10.1007/s13238-021-00876-1
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2543451-2
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  • 4
    Online Resource
    Online Resource
    Blood‐Glucose‐Powered Metabolic Fuel Cell for Self‐Sufficient Bioelectronics
    Wiley ; 2023
    In:  Advanced Materials Vol. 35, No. 21 ( 2023-05)
    Details
    In: Advanced Materials, Wiley, Vol. 35, No. 21 ( 2023-05)
    Abstract: Currently available bioelectronic devices consume too much power to be continuously operated on rechargeable batteries, and are often powered wirelessly, with attendant issues regarding reliability, convenience, and mobility. Thus, the availability of a robust, self‐sufficient, implantable electrical power generator that works under physiological conditions would be transformative for many applications, from driving bioelectronic implants and prostheses to programing cellular behavior and patients’ metabolism. Here, capitalizing on a new copper‐containing, conductively tuned 3D carbon nanotube composite, an implantable blood‐glucose‐powered metabolic fuel cell is designed that continuously monitors blood‐glucose levels, converts excess glucose into electrical power during hyperglycemia, and produces sufficient energy (0.7 mW cm −2 , 0.9 V, 50 m m glucose) to drive opto‐ and electro‐genetic regulation of vesicular insulin release from engineered beta cells. It is shown that this integration of blood‐glucose monitoring with elimination of excessive blood glucose by combined electro‐metabolic conversion and insulin‐release‐mediated cellular consumption enables the metabolic fuel cell to restore blood‐glucose homeostasis in an automatic, self‐sufficient, and closed‐loop manner in an experimental model of type‐1 diabetes.
    Type of Medium: Online Resource
    ISSN: 0935-9648 , 1521-4095
    URL: Issue
    URL: Article
    DOI: 10.1002/adma.v35.21
    DOI: 10.1002/adma.202300890
    RVK:
    UA 1538
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1474949-X
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  • 5
    Online Resource
    Online Resource
    Sunlight‐Controllable Biopharmaceutical Production for Remote Emergency Supply of Directly Injectable Therapeutic Proteins
    Wiley ; 2022
    In:  Small Vol. 18, No. 41 ( 2022-10)
    Details
    In: Small, Wiley, Vol. 18, No. 41 ( 2022-10)
    Abstract: Biopharmaceutical manufacturing requires specialized facilities and a long‐range cold supply chain for the delivery of the therapeutics to patients. In order to produce biopharmaceuticals in locations lacking such infrastructure, a production process is designed that utilizes the trigger‐inducible release of large quantities of a stored therapeutic protein from engineered endocrine cells within minutes to generate a directly injectable saline solution of the protein. To illustrate the versatility of this approach, it is shown that not only insulin, but also glucagon‐like peptide 1 (GLP‐1), nanoluciferase (NLuc), and the model biopharmaceutical erythropoietin (EPO) can be trigger‐inducibly released, even when using biologically inactive insulin as a carrier. The facilitating beta cells are engineered with a controllable TRPV1‐mediated Ca 2+ influx that induces the fusion of cytoplasmic storage vesicles with the membrane, leading to the release of the stored protein. When required, the growth medium is exchanged for saline solution, and the system is stimulated with the small molecule capsaicin, with a hand‐warming pack, or simply by using sunlight. Injection of insulin saline solution obtained in this way into a type‐1 diabetes mouse model results in the regulation of blood glucose levels. It is believed that this system will be readily adaptable to deliver various biopharmaceutical proteins at remote locations.
    Type of Medium: Online Resource
    ISSN: 1613-6810 , 1613-6829
    URL: Issue
    URL: Article
    DOI: 10.1002/smll.v18.41
    DOI: 10.1002/smll.202202566
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2168935-0
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  • 6
    Online Resource
    Online Resource
    Phosphoregulated orthogonal signal transduction in mammalian cells
    Springer Science and Business Media LLC ; 2020
    In:  Nature Communications Vol. 11, No. 1 ( 2020-06-18)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-06-18)
    Abstract: Orthogonal tools for controlling protein function by post-translational modifications open up new possibilities for protein circuit engineering in synthetic biology. Phosphoregulation is a key mechanism of signal processing in all kingdoms of life, but tools to control the involved processes are very limited. Here, we repurpose components of bacterial two-component systems (TCSs) for chemically induced phosphotransfer in mammalian cells. TCSs are the most abundant multi-component signal-processing units in bacteria, but are not found in the animal kingdom. The presented phosphoregulated orthogonal signal transduction (POST) system uses induced nanobody dimerization to regulate the trans-autophosphorylation activity of engineered histidine kinases. Engineered response regulators use the phosphohistidine residue as a substrate to autophosphorylate an aspartate residue, inducing their own homodimerization. We verify this approach by demonstrating control of gene expression with engineered, dimerization-dependent transcription factors and propose a phosphoregulated relay system of protein dimerization as a basic building block for next-generation protein circuits.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-020-16895-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
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  • 7
    Online Resource
    Online Resource
    Genetically Encoded Protein Thermometer Enables Precise Electrothermal Control of Transgene Expression
    Wiley ; 2021
    In:  Advanced Science Vol. 8, No. 21 ( 2021-11)
    Details
    In: Advanced Science, Wiley, Vol. 8, No. 21 ( 2021-11)
    Abstract: Body temperature is maintained at around 37 °C in humans, but may rise to 40 °C or more during high‐grade fever, which occurs in most adults who are seriously ill. However, endogenous temperature sensors, such as ion channels and heat‐shock promoters, are fully activated only at noxious temperatures above this range, making them unsuitable for medical applications. Here, a genetically encoded protein thermometer (human enhanced gene activation thermometer; HEAT) is designed that can trigger transgene expression in the range of 37–40 °C by linking a mutant coiled‐coil temperature‐responsive protein sensor to a synthetic transcription factor. To validate the construct, a HEAT‐transgenic monoclonal human cell line, FeverSense, is generated and it is confirmed that it works as a fever sensor that can temperature‐ and exposure‐time‐dependently trigger reporter gene expression in vitro and in vivo. For translational proof of concept, microencapsulated designer cells stably expressing a HEAT‐controlled insulin production cassette in a mouse model of type‐1 diabetes are subcutaneously implanted and topical heating patches are used to apply heat corresponding to a warm sensation in humans. Insulin release is induced, restoring normoglycemia. Thus, HEAT appears to be suitable for practical electrothermal control of cell‐based therapy, and may also have potential for next‐generation treatment of fever‐associated medical conditions.
    Type of Medium: Online Resource
    ISSN: 2198-3844 , 2198-3844
    URL: Issue
    URL: Article
    DOI: 10.1002/advs.v8.21
    DOI: 10.1002/advs.202101813
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2808093-2
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  • 8
    Online Resource
    Online Resource
    Smartphone‐Flashlight‐Mediated Remote Control of Rapid Insulin Secretion Restores Glucose Homeostasis in Experimental Type‐1 Diabetes
    Wiley ; 2021
    In:  Small Vol. 17, No. 35 ( 2021-09)
    Details
    In: Small, Wiley, Vol. 17, No. 35 ( 2021-09)
    Abstract: Emerging digital assessment of biomarkers by linking health‐related data obtained from wearable electronic devices and embedded health and fitness sensors in smartphones is opening up the possibility of creating a continuous remote‐monitoring platform for disease management. It is considered that the built‐in flashlight of smartphones may be utilized to remotely program genetically engineered designer cells for on‐demand delivery of protein‐based therapeutics. Here, the authors present smartphone‐induced insulin release in β‐cell line (iβ‐cell) technology for traceless light‐triggered rapid insulin secretion, employing the light‐activatable receptor melanopsin to induce calcium influx and membrane depolarization upon illumination. This iβ‐cell‐based system enables repeated, reversible secretion of insulin within 15 min in response to light stimulation, with a high induction fold both in vitro and in vivo. It is shown that programmable percutaneous remote control of implanted microencapsulated iβ‐cells with a smartphone's flashlight rapidly reverses hyperglycemia in a mouse model of type‐1 diabetes.
    Type of Medium: Online Resource
    ISSN: 1613-6810 , 1613-6829
    URL: Issue
    URL: Article
    DOI: 10.1002/smll.v17.35
    DOI: 10.1002/smll.202101939
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2168935-0
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  • 9
    Online Resource
    Online Resource
    Electrogenetics: Bridging synthetic biology and electronics to remotely control the behavior of mammalian designer cells
    Elsevier BV ; 2022
    In:  Current Opinion in Chemical Biology Vol. 68 ( 2022-06), p. 102151-
    Details
    In: Current Opinion in Chemical Biology, Elsevier BV, Vol. 68 ( 2022-06), p. 102151-
    Type of Medium: Online Resource
    ISSN: 1367-5931
    URL: Article
    DOI: 10.1016/j.cbpa.2022.102151
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2019216-2
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Design of programmable post-translational switch control platform for on-demand protein secretion in mammalian cells
    Oxford University Press (OUP) ; 2023
    In:  Nucleic Acids Research Vol. 51, No. 1 ( 2023-01-11), p. e1-e1
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 51, No. 1 ( 2023-01-11), p. e1-e1
    Abstract: The development of novel strategies to program cellular behaviors is a central goal in synthetic biology, and post-translational control mediated by engineered protein circuits is a particularly attractive approach to achieve rapid protein secretion on demand. We have developed a programmable protease-mediated post-translational switch (POSH) control platform composed of a chimeric protein unit that consists of a protein of interest fused via a transmembrane domain to a cleavable ER-retention signal, together with two cytosolic inducer-sensitive split protease components. The protease components combine in the presence of the specific inducer to generate active protease, which cleaves the ER-retention signal, releasing the transmembrane-domain-linked protein for trafficking to the trans-Golgi region. A furin site placed downstream of the protein ensures cleavage and subsequent secretion of the desired protein. We show that stimuli ranging from plant-derived, clinically compatible chemicals to remotely controllable inducers such as light and electrostimulation can program protein secretion in various POSH-engineered designer mammalian cells. As proof-of-concept, an all-in-one POSH control plasmid encoding insulin and abscisic acid-activatable split protease units was hydrodynamically transfected into the liver of type-1 diabetic mice. Induction with abscisic acid attenuated glycemic excursions in glucose-tolerance tests. Increased blood levels of insulin were maintained for 12 days.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkac916
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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