Mammalian synthetic biology in the age of genome editing and personalized medicine

Ho, Patrick; Chen, Yvonne Y.

doi:10.1016/j.cbpa.2017.06.003

Cited by 13 publications

(10 citation statements)

References 63 publications

(81 reference statements)

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“…The ability to reliably predict and program cellular decisions is a central goal in mammalian synthetic biology (Black et al, 2017;Ho and Chen, 2017;Kitada et al, 2018;Lienert et al, 2014;Prochazka et al, 2017;Xie and Fussenegger, 2015). This capability is critical for both understanding how changes to the cell state and cellular inputs drive cell fate changes, as well as for engineering cell-based therapies.…”

Section: The Cell As a Processormentioning

confidence: 99%

Context-aware synthetic biology by controller design: Engineering the mammalian cell

2021

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Section: The Cell As a Processormentioning

confidence: 99%

Context-aware synthetic biology by controller design: Engineering the mammalian cell

2021

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“…Given the high efficiency and precise targeting, CRISPR/Cas9 is regarded as the most powerful genome editing toolkit for dissection of molecular mechanisms and control of gene expression (Xu and Qi, 2018). Particularly, it has exhibited great potential in synthetic biology for cell reprogramming, protein engineering and circuitry design (Fellmann et al, 2017; Ho and Chen, 2017), and also for microbial metabolic engineering and manipulation of genetically intractable microorganisms (Cho et al, 2018b; Shapiro et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Multi-Layer Controls of Cas9 Activity Coupled With ATP Synthase Over-Expression for Efficient Genome Editing in Streptomyces

Wang

Zhao

Liu

et al. 2019

Front. Bioeng. Biotechnol.

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Efficient genome editing is a prerequisite of genetic engineering in synthetic biology, which has been recently achieved by the powerful CRISPR/Cas9 system. However, the toxicity of Cas9, due to its abundant intracellular expression, has impeded its extensive applications. Here we constructed a genetic cassette with triple controls of Cas9 activities at transcriptional, translational and protein levels, together with over-expression of the ATP synthase β-subunit AtpD, for the efficient genome editing in Streptomyces. By deletion of actII-ORF4 in Streptomyces coelicolor as a model, we found that constitutive expression of cas9 had about 90% editing efficiency but dramatically reduced transformation efficiency by 900-fold. However, triple controls of Cas9 under non-induction conditions to reduce its activity increased transformation efficiency over 250-fold, and had about 10% editing efficiency if combined with atpD overexpression. Overall, our strategy accounts for about 30-fold increased possibility for successful genome editing under the non-induction condition. In addition, about 80% editing efficiency was observed at the actII-ORF4 locus after simultaneous induction with thiostrepton, theophylline and blue light for Cas9 activity reconstitution. This improved straightforward efficient genome editing was also confirmed in another locus redD. Thus, we developed a new strategy for efficient genome editing, and it could be readily and widely adaptable to other Streptomyces species to improve genetic manipulation for rapid strain engineering in Streptomyces synthetic biology, due to the highly conserved genetic cassettes in this genus.

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“…Whereas recent mammalian theranostics have centred on therapeutic T cells, mammalian theranostic cells have also been developed for an array of other diseases 91 , 93 , 134 , 135 . Although these have not yet been developed for clinical use, they have shown great potential in preclinical studies, particularly for the treatment of autoimmune diseases.…”

Section: Mammalian Therapeuticsmentioning

confidence: 99%

Theranostic cells: emerging clinical applications of synthetic biology

McNerney

Doiron

et al. 2021

Nat Rev Genet

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Synthetic biology seeks to redesign biological systems to perform novel functions in a predictable manner. Recent advances in bacterial and mammalian cell engineering include the development of cells that function in biological samples or within the body as minimally invasive diagnostics or theranostics for the real-time regulation of complex diseased states. Ex vivo and in vivo cell-based biosensors and therapeutics have been developed to target a wide range of diseases including cancer, microbiome dysbiosis and autoimmune and metabolic diseases. While probiotic therapies have advanced to clinical trials, chimeric antigen receptor (CAR) T cell therapies have received regulatory approval, exemplifying the clinical potential of cellular therapies. This Review discusses preclinical and clinical applications of bacterial and mammalian sensing and drug delivery platforms as well as the underlying biological designs that could enable new classes of cell diagnostics and therapeutics. Additionally, we describe challenges that must be overcome for more rapid and safer clinical use of engineered systems.

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Mammalian synthetic biology in the age of genome editing and personalized medicine

Cited by 13 publications

References 63 publications

Context-aware synthetic biology by controller design: Engineering the mammalian cell

Context-aware synthetic biology by controller design: Engineering the mammalian cell

Multi-Layer Controls of Cas9 Activity Coupled With ATP Synthase Over-Expression for Efficient Genome Editing in Streptomyces

Theranostic cells: emerging clinical applications of synthetic biology

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