Synthetic DNA spike-ins (SDSIs) enable sample tracking and detection of inter-sample contamination in SARS-CoV-2 sequencing workflows

AbstractThe implementation of applied engineering principles to create synthetic biological systems promises to revolutionize medicine, but application of fundamentally redesigned organisms has thus far not impacted practical drug development. Here we utilize an engineered microbial organism with a six-letter semi-synthetic DNA code to generate a library of site-specific, click chemistry compatible amino acid substitutions in the human cytokine IL-2. Targeted covalent modification of IL-2 variants with PEG polymers and screening identifies compounds with distinct IL-2 receptor specificities and improved pharmacological properties. One variant, termed THOR-707, selectively engages the IL-2 receptor beta/gamma complex without engagement of the IL-2 receptor alpha. In mice, administration of THOR-707 results in large-scale activation and amplification of CD8+ T cells and NK cells, without Treg expansion characteristic of IL-2. In syngeneic B16-F10 tumor-bearing mice, THOR-707 enhances drug accumulation in the tumor tissue, stimulates tumor-infiltrating CD8+ T and NK cells, and leads to a dose-dependent reduction of tumor growth. These results support further characterization of the immune modulatory, anti-tumor properties of THOR-707 and represent a fundamental advance in the application of synthetic biology to medicine, leveraging engineered semi-synthetic organisms as cellular factories to facilitate discovery and production of differentiated classes of chemically modified biologics.

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Genetically Encoded RNA Nanodevices for Cellular Imaging and Regulation

Nanoscale ◽

10.1039/d0nr08301a ◽

2021 ◽

Author(s):

Qikun Yu ◽

Kewei Ren ◽

Mingxu You

Keyword(s):

Nucleic Acid ◽

Cellular Imaging ◽

Synthetic Dna

Nucleic acid-based nanodevices have been widely used in the fields of biosensing and nanomedicine. Traditionally, the majority of these nanodevices were first constructed in vitro using synthetic DNA or RNA...

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DNA-based self-assembly of nanostructures

10.1093/oxfordhb/9780199533053.013.24 ◽

2017 ◽

Author(s):

Joshua D. Carter ◽

Chenxiang Lin ◽

Yan Liu ◽

Hao Yan ◽

Thomas H. LaBean

Keyword(s):

Self Assembly ◽

Materials Science ◽

Directed Assembly ◽

Building Blocks ◽

Hierarchical Assembly ◽

Synthetic Dna ◽

Nanoscale Manufacturing ◽

Covalently Linked ◽

Design Construction ◽

Proteins And Peptides

This article examines the DNA-based self-assembly of nanostructures. It first reviews the development of DNA self-assembly and DNA-directed assembly, focusing on the main strategies and building blocks available in the modern molecular construction toolbox, including the design, construction, and analysis of nanostructures composed entirely of synthetic DNA, as well as origami nanostructures formed from a mixture of synthetic and biological DNA. In particular, it considers the stepwise covalent synthesis of DNA nanomaterials, unmediated assembly of DNA nanomaterials, hierarchical assembly, nucleated assembly, and algorithmic assembly. It then discusses DNA-directed assembly of heteromaterials such as proteins and peptides, gold nanoparticles, and multicomponent nanostructures. It also describes the use of complementary DNA cohesion as 'smart glue' for bringing together covalently linked functional groups, biomolecules, and nanomaterials. Finally, it evaluates the potential future of DNA-based self-assembly for nanoscale manufacturing for applications in medicine, electronics, photonics, and materials science.

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