This Week in Synthetic Biology #4

SHERLOCK diagnoses Ebola, genome-integrated circuits are stable for weeks, and survey are kinda OK with germline editing?

Good morning. This week…

Kaitlin Sullivan wrote a beautiful article for Grow by Ginkgo about how synthetic biology can help heal the earth after devastation, WIRED covered lab-grown breast milk, a new study suggests that men are twice as likely to support germline editing than women, and FoldIt released Education Mode, “a series of interactive three-dimensional biochemistry puzzles.” Sounds like a fun weekend activity for the whole family!

Meanwhile, Alexander Titus featured Michelle Rozo, principal director for biotechnology at the DoD, on his podcast, The Scientist wrote about cell-free systems and how they can help fight the pandemic, an entire Netflix series was stored in DNA, and an interview with Chris Hsu at GSK begs the question: is a PhD necessary in biotech?

In academic news, researchers at Penn State received $1.2 million from the NSF to bring an enhanced gene editing method to vertebrates, a team at the University of Texas at Austin nabbed a U.S. Army grant to develop insect-inspired biomaterials, and UCSF bioengineers are racing to launch AeroNabs, an aerosolized “designer” nanobody that fights SARS-CoV-2.

This Week in Synthetic Biology is brought to you by Niko McCarty and http://Bioeconomy.XYZ.

This week in research…

(featuring open-access articles!)

Where is That Noise Coming From!?! (Open Access)

Gene expression in cells is “noise-y”. Protein levels vary from one cell to the next, even if those cells are genetically identical and are grown in the same environment. To find the source of this “noise”, the Bleris lab has teased apart “gene expression at the transcriptional, translational, and post-translational level using custom engineered circuits stably integrated in human cells using CRISPR”. The study, published in Nucleic Acids Research, shows that most noise comes from transcription.

Stable Genetic Circuits in E. coli (Open Access)

The Voigt lab is back, with a new study in Molecular Systems Biology. They “designed genomic landing pads in E. coli at high-expression sites” that are stable for weeks, without selection. Their integrated circuits also required fourfold less RNA polymerase compared to those same circuits on plasmids.

Diagnosing Ebola and Lassa cases in real-time (Open Access)

Viral hemorrhagic fevers demand rapid diagnostics, and CRISPR-based systems are quickly emerging as the victor. A new study, with dozens of contributing labs, shows that Cas13a (SHERLOCK, specifically) can diagnose Ebola and Lassa viruses with 100% sensitivity. The team even developed a mobile application to quickly report results, and deployed the tech in Sierra Leone and Nigeria. The work was published in Nature Communications.

Cas13a Detects Small Molecules (Open Access)

Cas13a is more versatile than you think. In a separate study, Cas13a was modified to quantify the concentration of up to eight samples in a single reaction. The team, from the University of Colorado at Boulder, thinks that “hundreds of reactions can be easily quantified in a few hours”. The work is out now in Nucleic Acids Research.

Pow Pow! Knocking Out Herpes Virus in Mice (Open Access)

The Jerome lab at the University of Washington has used meganucleases — a type of restriction enzyme — to eliminate over 90% of latent herpes simplex virus in mice. They delivered the gene-editing proteins via adeno-associated viruses (AAVs), and found that a “triple AAV serotype combination” works best. The study was published in Nature Communications; check out the press release!

More research…

(including engineered vesicles for targeted CRISPR delivery and lots of other studies)

A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo by Chien, J.C. et al. in Nucleic Acids Research (Open Access)

A scalable CRISPR/Cas9-based fluorescent reporter assay to study DNA double-strand break repair choice by Roidos, P. et al. in Nature Communications (Open Access)

Cell-free synthesis of natural compounds from genomic DNA of biosynthetic gene clusters by Siebels, I. et al. in ACS Synthetic Biology.

CL6mN: Rationally designed optogenetic photoswitches with tunable dissociation dynamics by Mukherjee, A. et al. in ACS Synthetic Biology.

Conditional recruitment to a DNA-bound CRISPR–Cas complex using a colocalization-dependent protein switch by Kirkpatrick, R.L. et al. in ACS Synthetic Biology.

Constructing a novel biosynthetic pathway for the production of glycolate from glycerol in Escherichia coli by Zhan, T. et al. in ACS Synthetic Biology.

Creating CRISPR-responsive smart materials for diagnostics and programmable cargo release by Gayet, R.V. et al. in Nature Protocols.

CRISPR GUARD protects off-target sites from Cas9 nuclease activity using short guide RNAs by Coelho, M.A. et al. in Nature Communications (Open Access)

CRISPR-induced indels and base editing using the Staphylococcus aureus Cas9 in potato by Veillet, F. et al. in PLoS One. (Open Access)

CRISPRi-based dynamic regulation of hydrolase for synthesis of poly-γ-glutamic acid with variable molecular weights by Sha, Y. et al. in ACS Synthetic Biology.

CRISPR interference of nucleotide biosynthesis improves production of a single‐domain antibody in Escherichia coli by Landberg, J. et al. in Biotechnology and Bioengineering.

Designed protein logic to target cells with precise combinations of surface antigens by Lajoie, M.J. et al. in Science.

Developing rapid growing Bacillus subtilis for improved biochemical and recombinant protein production by Liu, Y. et al. in Metabolic Engineering Communications (Open Access)

Dynamic control of 4-hydroxyisoleucine biosynthesis by modified L-isoleucine biosensor in recombinant Corynebacterium glutamicum by Tan, S. et al. in ACS Synthetic Biology.

Engineering AvidCARs for combinatorial antigen recognition and reversible control of CAR function by Salzer, B. et al. in Nature Communications (Open Access)

Engineering DNA nanostructures for siRNA delivery in plants by Zhang, H. et al. in Nature Protocols.

Extracellular vesicles engineered with valency-controlled DNA nanostructures deliver CRISPR/Cas9 system for gene therapy by Zhuang, J. et al. in Nucleic Acids Research (Open Access)

Genome-wide specificity of dCpf1 cytidine base editors by Kim, D. et al. in Nature Communications (Open Access)

GOTI, a method to identify genome-wide off-target effects of genome editing in mouse embryos by Zuo, E. et al. in Nature Protocols.

High-level production of ornithine by expression of the feedback inhibition-insensitive N-acetyl glutamate kinase in the sake yeast Saccharomyces cerevisiae by Ohashi, M. et al. in Metabolic Engineering (Open Access)

Improved butanol production using FASII pathway in E. coli by Jawed, K. et al. in ACS Synthetic Biology.

Living, self‐replicating ferrofluids for fluidic transport by Mirkhani, N., Christiansen, M.G. and Schuerle, S. in Advanced Functional Materials.

Long-term rewritable report and recording of environmental stimuli in engineered bacterial populations by Zou, Z. and Ye, B. in ACS Synthetic Biology.

Optimizing bacteriophage engineering through an accelerated evolution platform by Favor, A.H. et al. in Scientific Reports (Open Access)

Photothermogenetic inhibition of cancer stemness by near-infrared-light-activatable nanocomplexes by Yu, Y. et al. in Nature Communications (Open Access)

Plasmid-based complementation of large deletions in Phaeodactylum tricornutum biosynthetic genes generated by Cas9 editing by Slattery, S.S. et al. in Scientific Reports (Open Access)

Rapid repair of human disease-specific single-nucleotide variants by One-SHOT genome editing by Yokouchi, Y. et al. in Scientific Reports (Open Access)

Rational design of a genetic finite state machine: Combining biology, engineering, and mathematics for bio-computer research by Fuente, D. et al. in Mathematics (Open Access)

Synthetic conversion of leaf chloroplasts into carotenoid-rich plastids reveals mechanistic basis of natural chromoplast development by Llorente, B. et al. in PNAS

The Genetic Code Kit: An open-source cell-free platform for biochemical and biotechnology education by Williams, L.C. et al. in Frontiers in Bioengineering and Biotechnology (Open Access)

Yarrowia lipolytica strains engineered for the production of terpenoids by Arnesen, J.A. et al. in Frontiers in Bioengineering and Biotechnology (Open Access)

This week in reviews and commentary…

Applications of CRISPR in microbial cell factory: From genome re-construction to metabolic network re-programming by Wu, K. et al. in ACS Synthetic Biology.

Control strategies to manage trade-offs during microbial production by Han, Y. and Zhang, F. in Current Opinion in Biotechnology (Open Access)

Directed evolution of CRISPR/Cas systems for precise gene editing by Liu, R. et al. in Trends in Biotechnology.

Engineered bacteria to report gut function: technologies and implementation by Tanna, T., Ramachanderan, R. and Platt, R.J. in Current Opinion in Microbiology (Open Access)

How synthetic biology can help bioremediation by Rylott, E.L. and Bruce, N.C. in Current Opinion in Chemical Biology.

Sc3.0: revamping and minimizing the yeast genome by Dai, J. et al. in Genome Biology (Open Access)

Yeast chromosomal engineering to improve industrially-relevant phenotypes by Jin, J., Jia, B. and Yuan, Y. in Current Opinion in Biotechnology.

This week in preprints…

A high-performance genetically encoded fluorescent biosensor for imaging physiological peroxynitrite by Chen, Z. et al. bioRxiv.

A modular RNA interference system for multiplexed gene regulation by Dwijayanti, A. et al. bioRxiv.

An antiviral self-replicating molecular heterotroph by Shapiro, A. et al. bioRxiv.

An inexpensive semi-automated sample processing pipeline for cell-free RNA by Moufarrej, M.N. and Quake, S.R. bioRxiv.

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential by Gai, J. et al. bioRxiv.

A toolkit to generate inducible and interconvertible Drosophila transgenes by Wendler, F. et al. bioRxiv.

Baculovirus-vectored precision delivery of large DNA cargoes in human genomes by Aulicino, F. et al. bioRxiv.

Converting Escherichia coli MG1655 into a chemical overproducer through inactivating defense system against exogenous DNA by Wang, J. et al. bioRxiv.

De Novo designed peptide and protein hairpins that self-assemble into sheets and nanoparticles by Galloway, J.M. et al. bioRxiv.

Design of synthetic human gut microbiome assembly and function by Clark, R.L. et al. bioRxiv.

Elucidation and refinement of synthetic receptor mechanisms by Edelstein, H. I. et al. bioRxiv.

Multidimensional single-cell benchmarking of inducible promoters for precise dynamic control in budding yeast by Gligorovski, V., Sadeghi, A. and Rahi, S.J. bioRxiv.

Programming animal physiology and behaviors through engineered bacteria by Gao, B. and Sun, Q. bioRxiv.

Quantitative profiling of microbial communities by de novo metaproteomics by Kleikamp, H.B.C. et al. bioRxiv.

This Week in Synthetic Biology is published every Friday, and covers the latest peer-reviewed research, preprints, and other news in the field. A version of these newsletters is also posted on and my website,

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