Building Coronaviruses

A new method to create and amplify SARS-CoV-2 mutants. Researchers made wild-type, mutagenized and fluorescent versions of the virus using de novo DNA synthesis.

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Good morning. Bacteria ‘size up’ their neighbors by carefully measuring small molecules and changing their population levels in response; it’s called quorum sensing. Now, a synthetic system enables the same in mammalian cells. A genetic circuit, responsive to auxin, controlled mammalian cell populations for up to 42 days, continuously. Also, a new method to create and amplify SARS-CoV-2 mutants. Researchers made wild-type, mutagenized and fluorescent versions of the virus using de novo DNA synthesis and cell transfections in kidney fibroblast cells. The whole process takes less than a month and can be used to build viruses for antiviral assays.

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Notable Papers

( * = open access, † = review article)

Synthetic mammalian signaling circuits for robust cell population control. Ma Y…Elowitz M.B. Cell.

*A simple reverse genetics method to generate recombinant coronaviruses. Mélade J…de Lamballerie X. EMBO Reports.

*Cell-specific regulation of gene expression using splicing-dependent frameshifting. Ling J.P…Blackshaw S. bioRxiv (preprint).

Transcriptional neighborhoods regulate transcript isoform lengths and expression levels. Brooks A.N…Steinmetz L.M. Science.

Basic Research

*Structural basis for mismatch surveillance by CRISPR–Cas9. Bravo J.P.K…Taylor D.W. Nature.

*Global chromosome rearrangement induced by CRISPR-Cas9 reshapes the genome and transcriptome of human cells. Liu Y…Guo Y. Nucleic Acids Research.

*A tRNA modifying enzyme as a tunable regulatory nexus for bacterial stress responses and virulence. Fleming B.A…Mulvey M.A. Nucleic Acids Research.

*Nanopore ReCappable sequencing maps SARS-CoV-2 5′ capping sites and provides new insights into the structure of sgRNAs. Ugolini C…Leonardi T. Nucleic Acids Research.

*Premature aging in mice with error-prone protein synthesis. Shcherbakov D…Böttger E.C. Science Advances.

*Crosstalk between CRISPR-Cas9 and the human transcriptome. Smargon A.A…Yeo G.W. Nature Communications.

*CRISPR/Cas13 effectors have differing extents of off-target effects that limit their utility in eukaryotic cells. Ai Y., Liang D. & Wilusz J.E. Nucleic Acids Research.

*Ultraefficient extracellular vesicle–guided direct reprogramming of fibroblasts into functional cardiomyocytes. Kim H…Kim S.H. Science Advances.


Urinary detection of early responses to checkpoint blockade and of resistance to it via protease-cleaved antibody-conjugated sensors. Mac Q.D…Kwong G.A. Nature Biomedical Engineering.

*Robust and tunable performance of a cell-free biosensor encapsulated in lipid vesicles. Boyd M.AKamat N.P. bioRxiv (preprint).

Metabolite-based biosensors for natural product discovery and overproduction. Shi S…Luo Y. Current Opinion in Biotechnology.


*Integrase-mediated differentiation circuits improve evolutionary stability of burdensome and toxic functions in E. coli. Williams R.L. & Murray R.M. bioRxiv (preprint).

Computation & Modelling

Modeling suggests gene editing combined with vaccination could eliminate a persistent disease in livestock. Petersen G.E.L…Doeschl-Wilson A. PNAS.

*Regulatory strategies to schedule threshold crossing of protein levels at a prescribed time. Nieto C. et al. bioRxiv (preprint).

*A parametric logistic equation with light flux and media concentration for cultivation planning of microalgae. Kambe K…Hori Y. bioRxiv (preprint).

*Regulation strategies for two-output biomolecular networks. Alexis E…Papachristodoulou A. bioRxiv (preprint).

RNA Compensation: A Positive Feedback Insulation Strategy for RNA-Based Transcription Networks. Liu B…Franco E. ACS Synthetic Biology.

*A feedback control principle common to several biological and engineered systems. Suen J.Y. & Navlakha S. Journal of the Royal Society Interface.

*Modelling of glucose repression signalling in yeast Saccharomyces cerevisiae. Persson S…Cvijovic M. FEMS Yeast Research.

DNA Assembly

*Development of a dedicated Golden Gate Assembly platform (RtGGA) for Rhodotorula toruloides. Bonturi N…Lahtvee P. bioRxiv (preprint).

Genetic Engineering

Efficient targeted insertion of large DNA fragments without DNA donors. Wang J…Yin H. Nature Methods.

*Inducible CRISPR/Cas9 allows for multiplexed and rapidly segregated single target genome editing in Synechocystis sp. PCC 6803. Cengic I…Hudson E.P. bioRxiv (preprint).

*Antispacer peptide nucleic acids for sequence-specific CRISPR-Cas9 modulation. Economos N.G…Glazer P.M. Nucleic Acids Research.

*Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing. O’Geen H…Segal D.J. Nucleic Acids Research.


Smart materials: rational design in biosystems via artificial intelligence. Sagdic K…Inci F. Trends in Biotechnology.

Medicine & Diagnostics

*Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. Balboa D…Otonkoski T. Nature Biotechnology.

*Designing sensitive viral diagnostics with machine learning. Metsky H.C…Sabeti P.C. Nature Biotechnology.

Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells. North K…Bradley R.K. Nature Biotechnology.

*Double knockout CRISPR screen in cancer resistance to T cell cytotoxicity. Park J.J…Chen S. bioRxiv (preprint).

Metabolic Engineering

Biosynthesis of β-lactam nuclei in yeast. Yang D…Sun Z. Metabolic Engineering.

Synthetic metabolic pathways for conversion of CO2 into secreted short-to medium-chain hydrocarbons using cyanobacteria. Yunus I.S…Jones P.R. Metabolic Engineering.

Improved methylation in E. coli via an efficient methyl supply system driven by betaine. Liu Q., Lin B & Tao Y. Metabolic Engineering.

Molecular Engineering

*Deep learning guided optimization of human antibody against SARS-CoV-2 variants with broad neutralization. Shan S…Peng J. PNAS.

Tools & Technology

Design of Synthetic Mammalian Promoters Using Highly Palindromic Subsequences. Govorkova P., Lam C.K.C. & Truong K. ACS Synthetic Biology.

Polymer Encapsulation of Bacterial Biosensors Enables Coculture with Mammalian Cells. Moya-Ramírez I…Polizzi K. ACS Synthetic Biology.

*Mutation-specific reporter for optimization and enrichment of prime editing. Schene I.F…Fuchs S.A. Nature Communications.

Identification of antimicrobial peptides from the human gut microbiome using deep learning. Ma Y…Wang J. Nature Biotechnology.

Tyto: A Python Tool Enabling Better Annotation Practices for Synthetic Biology Data-Sharing. Bartley B.A. ACS Synthetic Biology.


Bacterial biofilms as platforms engineered for diverse applications. Li Z…Wang F. Biotechnology Advances.

Smart microalgae farming with internet-of-things for sustainable agriculture. Lim H.R…Show P.L. Biotechnology Advances.

Until next time,