GM Mosquitoes in Florida: Index #5

A large team from the Vidyasirimedhi Institute of Science and Technology and the Broad Institute of MIT and Harvard have developed a SHERLOCK assay (which uses the Cas13 protein) to detect the RNA in SARS-CoV-2.

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Good morning. This week…

The EPA has approved Oxitec’s plan to release genetically-engineered mosquitoes into the Florida keys, the Netflix show "Biohackers” received mixed reviews, WIRED wrote about a clump of bacteria that survived in space for three years, and Katherine Wu wrote about “predatory bacteria” that hunt and eat living cells. As if microbes, in the middle of a pandemic, weren’t scary enough!

Desiree Ho, a student at UC Berkeley, wrote a fantastic article about the intersection of gene editing, paper, and art (check out the video; it’s worth your time), Popular Mechanics separated genetic engineering facts from fiction, Harris-Stowe State University will develop a Biotechnology Certificate program after receiving $342K from the NSF, and Ian Simon, a former biosecurity and biodefense policy analyst, was interviewed for Titus Talks.

In industry news, Synthego raised $100M for AI-driven gene editing, an open letter called on Beyond Meat and Impossible Foods to ditch GMO products (my bet: not going to happen), and TechCrunch wrote about investments in synthetic biology companies.

This Week in Synthetic Biology is part of Bioeconomy.XYZ. Let me know what you want to see in the next newsletter by sending a message on Twitter.

🧬This week in research…

A Cas13-Based Assay Detects SARS-CoV-2 (Open Access)

Tests for SARS-CoV-2—the coronavirus behind the disease COVID-19—could use some help. Now, a large team from the Vidyasirimedhi Institute of Science and Technology and the Broad Institute of MIT and Harvard have developed a SHERLOCK assay (which uses the Cas13 protein) to detect the RNA in SARS-CoV-2. The researchers collected 154 nasopharyngeal and throat swab samples from Siriraj Hospital, in Thailand, and showed that the assay “was 100% specific and 100% sensitive with a fluorescence readout.” It could detect as little as 42 RNA copies of the virus. The study was published in Nature Biomedical Engineering.

Multiplexed Genome Editing in Fruit Flies (Open Access)

The Boutros lab at Heidelberg University has, for the first time, used Cas12a to edit the fruit fly (Drosophila melanogaster) genome. Until now, scientists had only been able to use Cas9. The authors demonstrated that Cas12a from Lachnospiraceae bacterium—but not Acidaminococcus—were functional in the flies, and that the editing efficiency of the Cas12a protein could be tuned with temperature (with 29°C being the optimal). They were able to target up to 8 genes at once from a single crRNA array, and concluded the paper by reporting a mutated version of the Cas12a protein (D156R) with an improved editing efficiency. The study was published in PNAS.

Malaria Mosquito Gets Gene Drive Upgrade (Open Access)

In mosquito-related news, the James lab at UC-Irvine has developed a Cas9/guide RNA-based gene drive for Anopheles gambiae, one of the main species that transmit malaria. The new gene drive, which was reported in PNAS, targets the cardinal gene that encodes the red-eye phenotype. The gene drive spread to at least 98% of a population—both males and females—after only 6 to 10 generations in a cage trials, and mosquitoes resistant to the gene drive appeared at a frequency of less than 0.1%.

An Intercellular Signaling Toolbox for Cell–Cell Communication (Open Access)

Researchers at the Chinese Academy of Sciences have created an intercellular signaling “toolbox” that enables engineered cells to communicate with one another with minimal crosstalk. The work, published in Nature Communications, includes “biosynthesis gene clusters” that are used to build small signaling molecules within the cells, along with a suite of evolved transcription factors and engineered promoters, to increase the signal efficiency. The team demonstrated their “toolbox” in both yeast and human cells, performing complex bio-computations with up to seven engineered strains.

Baker Lab Creates ‘Designer’ Transmembrane Pores

At the University of Washington’s Institute for Protein Design, the papers never seem to stop. In another tour de force of computational protein design, the Baker lab has created transmembrane protein pores—made from concentric rings of α-helices—with a high selectivity for specific ions or molecules. A pore with 12 α-helices had a high selectivity for potassium ions, compared to sodium ions, while a pore with 16 α-helices enabled selective passage of biotinylated Alexa Fluor 488, a type of fluorescent dye. The study, published in Nature, could open the door for a range of designer channels and pores, with major applications for artificial cells.

Cell-Free System Produces Cannabinoids

Why grow cannabis—and pay the exorbitant energy bills—when you could crack open some cells and use enzymes instead? The Bowie lab at the UCLA-DOE Institute has created a cell-free system to produce cannabinoids; only 12 enzymes were needed to convert cheap, organic acids into cannabigerolic acid or cannabigerovarinic acid at a titer of about 0.5 grams per liter. That’s nearly two orders of magnitude higher than yeast-based production. The study, published in Nature Chemical Biology, could replace extraction of cannabinoids from plants in the future.

🧫 More research…

Activation of energy metabolism through growth media reformulation enables a 24-hour workflow for cell-free expression by Levine, M.Z. et al. in ACS Synthetic Biology.

An enumerative algorithm for de novo design of proteins with diverse pocket structures by Basanta, B. et al. in PNAS (Open Access)

A single Cas9-VPR nuclease for simultaneous gene activation, repression, and editing in Saccharomyces cerevisiae by Dong, C. et al. in ACS Synthetic Biology.

Cell‐free protein synthesis enables one‐pot cascade biotransformation in an aqueous‐organic biphasic system by Liu, W., Wu, C., Jewett, M.C. and Li, J. in Biotechnology and Bioengineering.

Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway by Johnston, C.W., Badran, A.H. and Collins, J.J. in Nature Communications (Open Access)

CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice by Wang, C. et al. in Science Translational Medicine (Open Access)

Display of functional nucleic acid polymerase on Escherichia coli surface and its application in directed polymerase evolution by Chung, M. et al. in Biotechnology and Bioengineering (Open Access)

Efficient selection scheme for incorporating noncanonical amino acids into proteins from Saccharomyces cerevisiae by Tang, H. et al. in Frontiers in Bioengineering and Biotechnology.

Engineering oleaginous yeast Yarrowia lipolytica for enhanced limonene production from xylose and lignocellulosic hydrolysate by Wei, L. et al. in FEMS Yeast Research.

Expanding the space of protein geometries by computational design of de novo fold families by Pan, X. et al. in Science.

Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing by Zhang, X. et al. in Science Advances (Open Access)

Homologous quorum sensing regulatory circuit (hQSRC): A dual-input genetic controller for modulating quorum sensing (QS)-mediated protein expression in E. coli by Hauk, P. et al. in ACS Synthetic Biology.

Isobutanol production freed from biological limits using synthetic biochemistry by Sherkhanov, S. et al. in Nature Communications (Open Access)

Multi-copy targeted integration for accelerated development of high-producing CHO cells by Sergeeva, D. et al. in ACS Synthetic Biology.

PINCER: improved CRISPR/Cas9 screening by efficient cleavage at conserved residues by Veeneman, B. et al. in Nucleic Acids Research (Open Access)

Rational design of minimal synthetic promoters for plants by Cai, Y. et al. in Nucleic Acids Research (Open Access)

Ribosomal synthesis and de novo discovery of bioactive foldamer peptides containing cyclic β-amino acids by Katoh, T. et al. in Nature Chemistry.

Ribosome-mediated polymerization of long chain carbon and cyclic amino acids into peptides in vitro by Lee, J. et al. in Nature Communications (Open Access)

SBML Level 3: an extensible format for the exchange and reuse of biological models by Keating, S.M. et al. in Molecular Systems Biology (Open Access)

Two-color imaging of non-repetitive endogenous loci in human cells by Tasan, I. et al. in ACS Synthetic Biology.

📓 This week in reviews and commentary…

Metabolic engineering strategies to overcome precursor limitations in isoprenoid biosynthesis by Zu Y., Prather K.L.J. and Stephanopoulos, G. in Current Opinion in Biotechnology.

On the “life-likeness” of synthetic cells by Damiano, L. and Stano, P. in Frontiers in Bioengineering and Biotechnology (Open Access)

🏍️ This week in preprints…

A computationally designed fluorescent biosensor for D-serine

A home and rescue gene drive forces its inheritance stably persisting in populations

An engineering theory of evolution

A single chromosome strain of S. cerevisiae exhibits diminished ethanol metabolism and tolerance

Attribution of genetic engineering: A practical and accurate machine-learning toolkit for biosecurity

CAR macrophages for SARS-CoV-2 immunotherapy

CAS-LiveFISH: Simple and versatile imaging of genomic loci in live mammalian cells and early pre-implantation embryos

Deep learning enables the design of functional de novo antimicrobial proteins

Extrinsic noise acts to lower protein production at higher translation initiation rates

Heterologous expression of cryptomaldamide in a cyanobacterial host

Multiplexed competition in a synthetic squid light organ microbiome using barcode-tagged gene deletions

Novel combination of CRISPR-based gene drives eliminates resistance and localises spread

One-step multiple site-specific base editing by direct embryo injection for precision and pyramid pig breeding

Potential for applying continuous directed evolution to plant enzymes

Predicting experimental designs leading to rewiring of transcription program and evolution of anticipatory regulation in E. coli

Recombinant SARS-CoV-2 RBD molecule with a T helper epitope as a built in adjuvant induces strong neutralization antibody response

The circadian oscillator analysed at the single-transcript level

Transcriptome-wide Cas13 guide RNA design for model organisms and viral RNA pathogens