Optoregulated Protein Release from an Engineered Living Material

Sankaran, Shrikrishnan; Campo, Aránzazu del

doi:10.26434/chemrxiv.6852617.v1

Cited by 3 publications

(3 citation statements)

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“…These strategies are based on the administration of material-embedded drug-producing bacteria or mammalian cells to provide sustained and patient-adapted delivery of therapeutic compounds. Recently, the Sankaran and Del Campo groups developed bacteria-based ELMs to produce therapeutic compounds in response to optical stimuli [ 274 , 275 ]. As host cells, endotoxin-free E. coli (ClearColi) were used, the outer membrane lipopolysaccharides of which have genetically been modified to avoid an endotoxin response in humans [ 276 ].…”

Section: Elmsmentioning

confidence: 99%

“…As host cells, endotoxin-free E. coli (ClearColi) were used, the outer membrane lipopolysaccharides of which have genetically been modified to avoid an endotoxin response in humans [ 276 ]. They transformed ClearColi with the blue light–responsive pDawn gene expression system to produce the red fluorescent protein as a model compound [ 274 ] or to express the vio-ABCE operon for the synthesis of the antimicrobial and antitumoral drug deoxyviolacein [ 275 ]. The engineered cells were embedded in either chemically crosslinked polyacrylamide or physically crosslinked agarose.…”

Section: Elmsmentioning

confidence: 99%

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Synthetic biology as driver for the biologization of materials sciences

Burgos-Morales

Gueye

Lacombe

et al. 2021

Materials Today Bio

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Materials in nature have fascinating properties that serve as a continuous source of inspiration for materials scientists. Accordingly, bio-mimetic and bio-inspired approaches have yielded remarkable structural and functional materials for a plethora of applications. Despite these advances, many properties of natural materials remain challenging or yet impossible to incorporate into synthetic materials. Natural materials are produced by living cells, which sense and process environmental cues and conditions by means of signaling and genetic programs, thereby controlling the biosynthesis, remodeling, functionalization, or degradation of the natural material. In this context, synthetic biology offers unique opportunities in materials sciences by providing direct access to the rational engineering of how a cell senses and processes environmental information and translates them into the properties and functions of materials. Here, we identify and review two main directions by which synthetic biology can be harnessed to provide new impulses for the biologization of the materials sciences: first, the engineering of cells to produce precursors for the subsequent synthesis of materials. This includes materials that are otherwise produced from petrochemical resources, but also materials where the bio-produced substances contribute unique properties and functions not existing in traditional materials. Second, engineered living materials that are formed or assembled by cells or in which cells contribute specific functions while remaining an integral part of the living composite material. We finally provide a perspective of future scientific directions of this promising area of research and discuss science policy that would be required to support research and development in this field.

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Section: Elmsmentioning

confidence: 99%

Section: Elmsmentioning

confidence: 99%

Synthetic biology as driver for the biologization of materials sciences

Burgos-Morales

Gueye

Lacombe

et al. 2021

Materials Today Bio

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“…A previous report using a red fluorescent protein showed that protein expression with the pDawn system is detectable after 1 -2 hours of pulse cycled irradiation. 24,44 We estimate that due to the weak autofluorescence of dVio, higher expression levels are necessary for detection. Increasing pulse cycles led to an increasing fluorescence in the exposed area which reaches a saturation value after 9 hours exposure (Figure 3b).…”

mentioning

confidence: 99%

Optoregulated Drug Release from an Engineered Living Hydrogel

Sankaran¹,

Becker²,

Wittmann³

et al. 2018

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In vitro evaluation of immune responses to bacterial hydrogels for the development of living therapeutic materials

Yanamandra

Bhusari

Campo

et al. 2022

Preprint

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In living therapeutic materials, organisms genetically programmed to produce and deliver drugs are encapsulated in porous matrices or hydrogels acting as physical barriers between the therapeutic organisms and the host cells. The therapeutic potential of such constructs has been highlighted in in vitro studies, but the translation to in vivo scenarios requires evaluation of the immune response to the presence of the encapsulated, living organisms. In this study, we investigate the responses of human peripheral blood mononuclear cells (PBMCs) exposed to a living therapeutic material consisting of engineered E. coli encapsulated in Pluronic F127-based hydrogels. The release of inflammation-related cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNFα and IFNγ) and cytotoxic proteins (granzyme A, granzyme B, perforin, granulysin, sFas, and sFasL) in response to the bacterial hydrogels, as well as the subsets of natural killer cells and T cells after exposure to the bacterial hydrogel for up to three days were examined. In direct contact with PBMCs, both E. coli and its endotoxin-free variant, ClearColi, induce apoptosis of the immune cells and trigger IL-6 release from the surviving cells. However, we found that encapsulation of the bacteria in Pluronic F127 diacrylate hydrogels considerably lowers their immunogenicity and practically abolishes apoptosis triggered by ClearColi. In comparison with E. coli, free and hydrogel-encapsulated ClearColi induced significantly lower levels of NK cell differentiation into the more cytolytic CD16dim subset. Our results demonstrate that ClearColi-encapsulated hydrogels generate low immunogenic response and are suitable candidates for the development of living therapeutic materials for in vivo testing to assess a potential clinical use. Nevertheless, we also observed a stronger immune response in pro-inflammatory PBMCs, possibly from donors with underlying infections. This suggests that including anti-inflammatory measures in living therapeutic material designs could be beneficial for such recipients.

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Optoregulated Protein Release from an Engineered Living Material

Cited by 3 publications

References 24 publications

Synthetic biology as driver for the biologization of materials sciences

Synthetic biology as driver for the biologization of materials sciences

Optoregulated Drug Release from an Engineered Living Hydrogel

In vitro evaluation of immune responses to bacterial hydrogels for the development of living therapeutic materials

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