Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics

Tan, Xiao; Letendre, Justin; Collins, James J.; Wong, Wilson

doi:10.1016/j.cell.2021.01.017

Cited by 81 publications

(75 citation statements)

References 197 publications

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“…The introduction of such materials will likely revolutionize the way how health and disease are managed. A glimpse of what could become clinical reality can be gained in recent review articles summarizing medically oriented pioneering work in synthetic biology [ 23 , 369 ].…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…Their partial reacquisition through horizontal gene transfer in certain rare insect lineages with extremely simple nutrient sources, such as sap or blood, enables them to host genome-reduced intracellular bacteria that provide other missing metabolites missing from these limited diets, and provides the "exception that proves the rule" 7 . Recent efforts in genome-scale synthesis [8][9][10] and genomewriting 11 have highlighted our increasing capacity to construct synthetic genomes with novel properties, thus providing a route to not only examine these interesting evolutionary questions but also yield new capacities of bioindustrial utility [12][13][14] .…”

Section: Main Textmentioning

confidence: 99%

“…Taken together, this demonstrates that pMTIV cells are biosynthesizing valine from core metabolites glucose and pyruvate, thereby representing successful metazoan biosynthesis of valine. Over the course of 3 passages in heavy valine-free medium, the non-essential amino acid alanine, which is absent from RPMI medium and synthesized from pyruvate, was found to be 86.1% 13 C-labeled in pMTIV cell lysates. Assuming similar turnover rates for alanine and valine within the CHO proteome, we expected to see similar percentages of 13 C-labeled valine.…”

Section: Ed6)mentioning

confidence: 99%

See 1 more Smart Citation

Resurrecting essential amino acid biosynthesis in a mammalian cell

Trolle¹,

McBee

Kaufman

et al. 2021

Preprint

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Major genomic deletions in independent eukaryotic lineages have led to repeated ancestral loss of biosynthesis pathways for nine of the twenty canonical amino acids1. While the evolutionary forces driving these polyphyletic deletion events are not well understood, the consequence is that extant metazoans are unable to produce nine essential amino acids (EAAs). Previous studies have highlighted that EAA biosynthesis tends to be more energetically costly2,3, raising the possibility that these pathways were lost from organisms with access to abundant EAAs in the environment4,5. It is unclear whether present-day metazoans can reaccept these pathways to resurrect biosynthetic capabilities that were lost long ago or whether evolution has rendered EAA pathways incompatible with metazoan metabolism. Here, we report progress on a large-scale synthetic genomics effort to reestablish EAA biosynthetic functionality in a mammalian cell. We designed codon-optimized biosynthesis pathways based on genes mined from Escherichia coli. These pathways were de novo synthesized in 3 kilobase chunks, assembled in yeasto and genomically integrated into a Chinese Hamster Ovary (CHO) cell line. One synthetic pathway produced valine at a sufficient level for cell viability and proliferation, and thus represents a successful example of metazoan EAA biosynthesis restoration. This prototrophic CHO line grows in valine-free medium, and metabolomics using labeled precursors verified de novo biosynthesis of valine. RNA-seq profiling of the valine prototrophic CHO line showed that the synthetic pathway minimally disrupted the cellular transcriptome. Furthermore, valine prototrophic cells exhibited transcriptional signatures associated with rescue from nutritional starvation. This work demonstrates that mammalian metabolism is amenable to restoration of ancient core pathways, thus paving a path for genome-scale efforts to synthetically restore metabolic functions to the metazoan lineage.

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“…-Ándale, puedo trabajar en algo así, pero en realidad la biología sintética se encarga del diseño o rediseño racional, usando, caracterizando y reutilizando partes moleculares en sistemas biológicos para proveerlos con una función mejorada o nueva para diversas aplicaciones (Tan et al, 2021). Esto es, explota la re-programación celular para obtener algún determinado bien -explicó Frank.…”

Section: Rompiendo El Hielo En El Gimnasiounclassified

Conversando de biología sintética en el gimnasio

Amores

2021

RDU

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a Distancia (CUAIEED) Este es un artículo de acceso abierto bajo la licencia de Creative Commons 4.0 Conversando de biología sintética en el gimnasio Gerardo Ruiź Amores ResumenLa biotecnología moderna, con el uso de herramientas desarrolladas en la ingeniería genética y la biología sintética, produce bienes biológicos funcionales en salud, alimentación, industria, medicina, entre otros. Algunos países de Europa, Asia, Norteamérica y Sudamérica son líderes en este campo, en donde el interés en el análisis de riesgos, así como en el registro de patentes de las tecnologías generadas fortalecen sus aplicaciones y redituabilidad. En México, se invierte en investigación; sin embargo, esperamos a que la tecnología generada por otros países llegue pronto. En este contexto, dos personas hacen amistad al conocerse en el gimnasio. Mario, un abogado sociable, y Frank, una persona un poco inusual. Frank responde las inquietudes de Mario referentes a qué y cómo se hace biología sintética. Finalmente, estos personajes coinciden en que México tiene espíritu emprendedor, creatividad y una economía en desarrollo, y que la competitividad se conseguirá por la apropiada administración de recursos, la inclusión de la sociedad en la ciencia, el impartir prácticas bioéticas desde temprano en la educación y mejores políticas.

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Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics

Cited by 81 publications

References 197 publications

Synthetic biology as driver for the biologization of materials sciences

Synthetic biology as driver for the biologization of materials sciences

Resurrecting essential amino acid biosynthesis in a mammalian cell

Conversando de biología sintética en el gimnasio

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