A Synthetic Optogenetic Transcription Device Enhances Blood-Glucose Homeostasis in Mice

  title={A Synthetic Optogenetic Transcription Device Enhances Blood-Glucose Homeostasis in Mice},
  author={Haifeng Ye and Marie Daoud-El Baba and Ren-Wang Peng and Martin Fussenegger},
  pages={1565 - 1568}
An implanted device using blue-light–triggered expression of the glucagon-like peptide 1 attenuates diabetes in mice. Synthetic biology has advanced the design of genetic devices that can be used to reprogram metabolic activities in mammalian cells. By functionally linking the signal transduction of melanopsin to the control circuit of the nuclear factor of activated T cells, we have designed a synthetic signaling cascade enabling light-inducible transgene expression in different cell lines… 

Externally-Controlled Systems for Immunotherapy: From Bench to Bedside

The aim is to develop smart immunogene therapy-based-ATMPs, which can be controlled by the addition of innocuous drugs or agents, allowing the clinicians to manage the intensity and durability of the therapy.

Engineering of synthetic gene networks for restoring homeostasis in experimental chronic diseases and their validation in patient-derived whole blood cultures

A mammalian cell synthetic cytokine converter is designed that quantifies psoriasis-associated TNF and IL22 levels using serially linked receptor-based synthetic signaling cascades, processes the levels of these proinflammatory cytokines with AND-gate logic, and triggers the corresponding expression of therapeutic levels of the anti-inflammatory/psoriatic cytokines IL4 and IL10, which have been shown to be immunomodulatory in patients.

Spatiotemporal Control of Gene Expression in Mammalian Cells and in Mice Using the LightOn System

Protocols for precise control of gene expression in mammalian cells and mice using the LightOn system are described, which consists of a single chimeric protein (GAVPO) that can homodimerize and bind to promoters upon exposure to blue light, activating transcription of a target gene.

Biomedically relevant circuit-design strategies in mammalian synthetic biology

This review addresses recent progress in mammalian synthetic biology circuit design and focuses on how novel designs push synthetic biology toward clinical implementation, as particularly optogenetics provides unprecedented opportunities for clinical application.

Optogenetic Medicine: Synthetic Therapeutic Solutions Precision-Guided by Light.

This review introduces 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 optogenetics systems into portable personalized precision bioelectronics medical tools.

Pharmaceutically controlled designer circuit for the treatment of the metabolic syndrome

A unique therapeutic strategy in which the clinically licensed antihypertensive drug guanabenz activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin is designed, able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia.

Tools and applications in synthetic biology.

Rethinking risk assessment for emerging technology first-in-human trials

How a misunderstanding of the concept of risk, and the possibilities and limitations of risk assessment, respectively, might impair decision-making by the relevant regulatory authorities and research ethics committees are highlighted, and possible solutions to tackle the issue are discussed.

Synthetic therapeutic gene circuits in mammalian cells




Controlling transgene expression in subcutaneous implants using a skin lotion containing the apple metabolite phloretin

The engineered mammalian phloretin-adjustable control element (PEACE) enabled adjustable and reversible transgene expression in different mammalian cell lines and primary cells and could foster advances in biopharmaceutical manufacturing as well as gene- and cell-based therapies.

Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin.

  • Yingbin FuH. Zhong K. Yau
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
Study of mice lacking RPE65, a protein essential for the regeneration of rod and cone pigments, and exogenous all-trans-retinal was also able to rescue the low sensitivity of rpe65-/- ipRGCs suggest melanopsin could be a bistable pigment.

Role of Melanopsin in Circadian Responses to Light

Although melanopsin is not essential for the circadian clock to receive photic input, it contributes significantly to the magnitude of photic responses.

Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa

It is shown that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa.

Activation of flavin-containing oxidases underlies light-induced production of H2O2 in mammalian cells.

It is found that H2O2 originated in peroxisomes and mitochondria, and it was enhanced in cells overexpressing flavin-containing oxidases, and these results support the hypothesis that photoreduction of flavoproteins underlies light-induced production of H 2O2 in cells.

Channelrhodopsin-1: A Light-Gated Proton Channel in Green Algae

A complementary DNA sequence in the green alga Chlamydomonas reinhardtiithat encodes a microbial opsin-related protein, which is suggested to be Channelopsin-1, which shows homology to the light-activated proton pump bacteriorhodopsin.

Tissue-specific increases in endogenous all-trans retinoic acid: possible contributing factor in ethanol toxicity.

  • G. Wolf
  • Medicine, Biology
    Nutrition reviews
  • 2010
A new study has reported that ethanol toxicity in mice actually increased atRA concentration in certain tissues, including brain hippocampus, apparently due to a mobilization of hepatic retinyl esters that led to increased retinol and atRA in specific tissues.