Engineering Mammalian Designer Cells for the Treatment of Metabolic Diseases

Wang, Yidan; Wang, Meiyan; Dong, Kaili; Ye, Haifeng

doi:10.1002/biot.201700160

Cited by 9 publications

(13 citation statements)

References 90 publications

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“…Compared to chemically controlled systems or conventional genetic engineering methods, optogenetics provides far more flexible and precise spatial and temporal control of signaling dynamics, protein levels, and enzyme activity, with minimal side effects. [123] The rapidly growing number of available optogenetic tools offers an opportunity to synthetic biologists to choose the best approach and strategy for their particular purposes. [75] Thus, current work aims to employ the combination of optogenetics with designer cells to achieve precise control of therapeutic outputs by light (blue light, [21,62] red light, [134] infrared light, [60] or far-red light [135] ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, they developed a smartphonecontrolled optogenetic designer cell device that can semiautomatically monitor and control blood glucose homeostasis in diabetic mice. [19,123] A major step toward the application of optogenetics for next-generation synthetic biology-inspired medicine is mind-controlled gene expression, which was successfully implemented in mice by Folcher et al [60] They developed lightcontrolled designer cells by introducing light-activated bacterial BphG1 DGCL; this produces c-di-GMP, which triggers the stimulator of interferon genes (STING)-dependent expression of SEAP from a synthetic interferon-β promoter. c-di-GMP binds to a c-di-GMP-binding transcription factor, called BldD, which is fused to a transactivator domain (p65-VP64).…”

Section: Light-engineered Cells In Drug Discovery and Translational Mmentioning

confidence: 99%

“…Implants consisting of engineered microencapsulated designer cells have already been used to introduce photosensitive cells with predefined functions into the host body. [123] Designer cell implants are most often located in deeper layers of tissue where they can barely be reached by light from the outside. [82] Systems based on induced pluripotent stem cells (iPSC) or even primary cells (e.g., mesenchymal stem cells) should provide a new platform for the next generation of photosensitive designer cells, thereby reducing concerns and side effects associated with implantation of immortalized cell line-based designer cells.…”

Section: Challenges In Optogenetic-based Therapeutical Mammalian Syntmentioning

confidence: 99%

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Light‐Controlled Mammalian Cells and Their Therapeutic Applications in Synthetic Biology

2018

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Light-engineered Cells In Drug Discovery and Translational Mmentioning

confidence: 99%

Section: Challenges In Optogenetic-based Therapeutical Mammalian Syntmentioning

confidence: 99%

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Light‐Controlled Mammalian Cells and Their Therapeutic Applications in Synthetic Biology

2018

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“…This might not be as far from reality as you think. Technological development and applications of light-based bioelectronics, in the form of electronic devices that interface with optogenetics and biological systems, are already experiencing rapid growth (Kozai and Vazquez 2015;Shao et al 2017;Wang et al 2017). Indeed, the parallel growth of optogenetics and synthetic biology is generating great enthusiasm for innovative technology platforms with the potential to achieve precise spatiotemporal control and manipulation of cellular behaviors through light stimulation, both in vitro and in vivo (Pathak et al 2013).…”

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confidence: 99%

Optogenetic Medicine: Synthetic Therapeutic Solutions Precision-Guided by Light

Fussenegger

2018

Cold Spring Harb Perspect Med

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Gene-and cell-based therapies are well recognized as central pillars of next-generation medicine, but controllability remains a critical issue for clinical applications. In this context, optogenetics is opening up exciting new opportunities for precision-guided medicine by using illumination with light of appropriate intensity and wavelength as a trigger signal to achieve pinpoint spatiotemporal control of cellular activities, such as transgene expression. In this review, we highlight recent advances in optogenetics, focusing on devices for biomedical applications. We introduce the construction and applications of optogenetic-based biomedical tools to treat neurological diseases, diabetes, heart diseases, and cancer, as well as bioelectronic implants that combine light-interfaced electronic devices and optogenetic systems into portable personalized precision bioelectronic medical tools. Optogeneticsbased technology promises the capability to achieve traceless, remotely controlled precision dosing of an enormous range of therapeutic outputs. Finally, we discuss the prospects for optogenetic medicine, as well as some emerging challenges.

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“…Wang and colleagues [9] discuss the recent progress and challenges in engineering mammalian cells for the treatment of metabolic diseases. In a same spirit but completely different context, Dou and Bennett [10] discuss how synthetic biology can play a pivotal role in precise control of the gut microbiome dynamics, for health and medical applications.…”

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confidence: 99%

Synthetic Biology: Reports from CSHA 2016 and More

Takano

2018

Biotechnology Journal

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The past two decades have witnessed immense progress in synthetic biology, including development of tools for genetic manipulation, elucidation of design principles for designing robust gene circuits, tools to analyze dynamics of engineered cells, and application of engineered cells in diverse contexts. A Cold Spring Harbor Asia Conference on Synthetic Biology was held in Suzhou China, in November 2016, to showcase a subset of such developments.To highlight these progresses, the Biotechnology Journal invited a number of review research articles to form the basis of a special issue on Synthetic Biology.These articles illustrate the progress in multiple aspects. For example, it is well appreciated that a major application arm for synthetic biology is in the engineering of metabolic pathways for producing valuable products. In this framework, Okano and colleagues [1] engineer the Lactobacillus plantarum NCIMB 8826 to enhance production of optically pure L-lactic acid from raw starch by deletion of lactate dehydrogenase, and the operon encoding lactate racemase (larA-E), and furthermore introduced the alpha-amylase from Streptococcus bovis 148 to increase the production level and to obtain 98.6% of optically pure lactic acid. Liu and colleagues [2] use rational metabolic engineering to increase L-cysteine production by 14-fold in Escherichia coli by modifying transport, sulfur supply, enhance precursor pathway, and reduce L-cysteine degradation.Interestingly, Thomson and coworkers [3] dissect the quiescent (Q-Cell) E. coli, known to have enhanced production of 3-hydroxybutyrate, for its proteomics and metabolomics. This analysis has made it possible for the potential use of Q-cells as a production host for a wide range of chemical compounds. Similarly, Hirasawa and colleagues [4] have analyzed the transcriptome and metabolome of Corynebacterium glutamicum to understand the mechanism of penicillin-induced glutamic acid production. Another way to examine the metabolism of a production host is by perturbation of a metabolic steady-state and the detailed analysis of the subsequent metabolic response. Tröndle and coworkers [5] perturb the supply of substrate (e.g., phosphoenolpyruvate) in E. coli to understand its impact on Lphenylalanine production and identified substrate transporters as important aspects to consider. Importantly, this method can be applied to other compound processes.The engineering of diverse gene circuits depends on the development of well characterized parts and devices and the corresponding chassis cells. To this end, McCutcheon and colleagues [6] demonstrate the development of a set of CRISPRCas-based devices for tunable control of gene expression. Aparicio and colleagues [7] use a CRISPR-Cas9 system to enable effective genetic engineering of Pseudomonas putida, which is emerging as an increasingly popular cell-factory platform for metabolic engineering and recombinant protein synthesis.Microfluidics has become an indispensable tool in quantitative analysis of single cells or cell populations. It...

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Engineering Mammalian Designer Cells for the Treatment of Metabolic Diseases

Cited by 9 publications

References 90 publications

Light‐Controlled Mammalian Cells and Their Therapeutic Applications in Synthetic Biology

Light‐Controlled Mammalian Cells and Their Therapeutic Applications in Synthetic Biology

Optogenetic Medicine: Synthetic Therapeutic Solutions Precision-Guided by Light

Synthetic Biology: Reports from CSHA 2016 and More

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