Synthetic Embryo, sans Egg & Sperm

Two studies this month have reported synthetic mouse embryos that can grow for 8.5 days without using eggs or sperm.

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Two studies this month have reported synthetic mouse embryos that can grow for 8.5 days without using eggs or sperm. News coverage has been surprisingly sparse (outside of the science journals), considering the massive implications and ethical consequences of this work.

The embryos were created by mixing stem cells and aerating them under Goldilocks-like conditions. My coverage won’t do the papers justice, but Nature wrote about them here (albeit focused on Magdalena Zernicka-Goetz’s paper, which was published after the efforts led by Jacob Hanna, in Cell, on August 1st).

Elsewhere: Genome editing can be directed to specific cell types by adding antibody fragments to the CRISPR delivery vehicle. This is nothing new: Prior work from Jennifer Doudna’s team showed that Cas9 particles are delivered solely to CD4+ T-cells when virus-like particles (the delivery vehicle) are tagged with HIV-1 glycoprotein. But in a preprint published this week, Doudna’s team expanded their “CRISPR-targeting” tools, demonstrating that antibody fragments, displayed on Cas9-enveloped particles, “target genome editing tools to specific cells.” The specificity persisted “even when target cells are rare (~2%) in the population.”

And finally, I’m co-author on a new paper in Nature Communications. We report a method to do simultaneous CRISPR activation and CRISPR inhibition in yeast cells, with up to 24 guide RNAs in parallel. We used this method to target “11 genes in central metabolism in a single transformation, achieving a 45-fold increase in succinic acid.” Oh yeah, and the whole thing is inducible, with low leakiness. We hope the tool will be broadly useful for prototyping metabolic engineering designs. I’ll write more about this paper soon. Thanks for reading.

Bio(tech) Index

(↑ = recommended article, * = open access, † = review, comment, etc. )

Basic Research

↑Synthetic embryos complete gastrulation to neurulation and organogenesis. Amadei G…Zernicka-Goetz M. Nature. Link

*R-loop formation and conformational activation mechanisms of Cas9. Pacesa M…Jinek M. Nature. Link

*Machine learning-assisted discovery of growth decision elements by relating bacterial population dynamics to environmental diversity. Aida H…Ying B-W. eLife. Link

*Real-time detection of response regulator phosphorylation dynamics in live bacteria. Butcher RJ & Tabor JJ. PNAS. Link

Biomanufacturing & Metabolic Engineering

*Improved cell-free transcription-translation reactions in microfluidic chemostats augmented with hydrogel membranes for continuous small molecule dialysis. Lavickova B, Grasemann L & Maerkl SJ. bioRxiv (preprint). Link

*Muconic acid production from glucose and xylose in Pseudomonas putida via evolution and metabolic engineering. Ling C…Beckham GT. Nature Communications. Link

Establishing an Autonomous Cascaded Artificial Dynamic (AutoCAD) regulation system for improved pathway performance. Jiang T…Yan Y. Metabolic Engineering. Link

*Optimizing E. coli as a formatotrophic platform for bioproduction via the reductive glycine pathway. Kim S…Lindner SN. bioRxiv (preprint). Link

Development of a nonauxotrophic L-homoserine hyperproducer in Escherichia coli by systems metabolic engineering. Cai M…Rao Z. Metabolic Engineering. Link

†Biowaste upcycling into second-generation microbial protein through mixed-culture fermentation. Areniello M…Lens PNL. Trends in Biotechnology. Link

↑*Engineering Pseudomonas putida KT2440 for chain length tailored free fatty acid and oleochemical production. Valencia LE…Keasling JD. bioRxiv (preprint). Link

*Construction of complete degradation pathway for nitrobenzene in Escherichia coli. Deng Y-D…Yao H. Ecotoxicology and Environmental Safety. Link

*Investigations into Metabolic Properties and Selected Nutritional Metabolic By-Products of Different Non-Saccharomyces Yeast Strains When Producing Non-alcoholic Beer. Methner Y…Jacob F. FEMS Yeast Research. Link


↑*La révolution de l’ADN: biocompatible and biosafe DNA data storage. Maes A…Lemaire SD. bioRxiv (preprint). Link

  • A French team reports a DNA data storage system that organizes information “on long double-stranded replicative DNA molecules” and has, theoretically, unlimited storage capacity. As a proof-of-concept, they store the full texts of “Declaration of the Rights of Man and of the Citizen of 1789 and the Declaration of the Rights of Woman and of the 5 Female Citizen published in 1791.” Each strip of DNA was then dried and stored in a metallic capsule, thus “ensuring their stability for thousands of years. The data could be read many times with 100% fidelity.”

Computational Tools & Models

*Context-Aware Technology Mapping in Genetic Design Automation. Engelmann N…Koeppl H. bioRxiv (preprint). Link

*DNAffinity: a machine-learning approach to predict DNA binding affinities of transcription factors. Barissi S…Orozco M. Nucleic Acids Research. Link

*A toolkit for enhanced reproducibility of RNASeq analysis for synthetic biologists. Garcia BJ…Eslami M. Synthetic Biology. Link

CRISPRCasStack: a stacking strategy-based ensemble learning framework for accurate identification of Cas proteins. Zhang T…Wang G. Briefings in Bioinformatics. Link

Taxonomic classification of DNA sequences beyond sequence similarity using deep neural networks. Mock F…Marz M. PNAS. Link

CRISPR & Gene Editing

↑*Inducible expression of large gRNA arrays for multiplexed CRISPRai applications. Shaw WM…Ledesma-Amaro R. Nature Communications. Link

↑Craspase is a CRISPR RNA-guided, RNA-activated protease. Hu C…Ke A. Science. Link

  • Well shit. Last week, I wrote about a preprint that showed Cas7-11 acts as an RNA-guided protease. But the same has already been shown, by a separate group, in a Science paper out this week! The mechanism — namely, the interactions between Cas7-11 and Csx29 / Csx30 — are confirmed via cryoEM.

↑*Structure and engineering of the minimal type VI CRISPR-Cas13bt3. Nakagawa R…Nureki O. Molecular Cell. Link

↑A sustainable mouse karyotype created by programmed chromosome fusion. Wang L-B…Li W. Science. Link

High-yield genome engineering in primary cells using a hybrid ssDNA repair template and small-molecule cocktails. Shy BR…Marson A. Nature Biotechnology. Link

*Enzymatic Supercoiling of Bacterial Chromosomes Facilitates Genome Manipulation. Fujita H…Su’etsugu M. ACS Synthetic Biology. Link

*Programmable RNA base editing with a single gRNA-free enzyme. Han W…Wang Z. Nucleic Acids Research. Link

*A Universal Approach to Gene Expression Engineering. Lale R…Hohmann-Marriott MF. Synthetic Biology. Link

Genetic Circuits

*Overcoming Leak Sensitivity in CRISPRi Circuits Using Antisense RNA Sequestration and Regulatory Feedback. Specht DA, Cortes LB & Lambert G. ACS Synthetic Biology. Link

A Universal Method for Developing Autoinduction Expression Systems Using AHL-Mediated Quorum-Sensing Circuits. Li L…Wen T. ACS Synthetic Biology. Link

Gene Synthesis & Assembly

↑*A nanopore interface for higher bandwidth DNA computing. Zhang K…Nivala J. Nature Communications. Link

Medicine & Diagnostics

A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection. Murphy SC…Kappe SHI. Science Translational Medicine. Link

*Deep mutational scanning identifies SARS-CoV-2 Nucleocapsid escape mutations of currently available rapid antigen tests. Frank F…Ortlund EA. Cell. Link

*Subgenomic particles in rAAV vectors result from DNA lesion/break and non-homologous end joining of vector genomes. Zhang J…Xiao W. Molecular Therapy: Nucleic Acid. Link

*STING-pathway modulation to enhance the immunogenicity of adenoviral-vectored vaccines. Padron-Regalado E…Spencer AJ. Scientific Reports. Link

*Data-Driven Design of Protein-Derived Peptide Multiplexes for Biomimetic Detection of Exhaled Breath VOC Profiles. Nakano-Baker O…MacKenzie JD. bioRxiv (preprint). Link

Preclinical evaluation of proteolytic targeting of LCK as a therapeutic approach in T cell acute lymphoblastic leukemia. Hu J…Yang JJ. Science Translational Medicine. Link

*Safety switch optimization enhances antibody-mediated elimination of CAR T cells. Shabaneh TB…Lajoie MJ. bioRxiv (preprint). Link

*Development of a human phage display-derived anti-PD-1 scFv antibody: an attractive tool for immune checkpoint therapy. Ghaderi SS…Sharifzadeh Z. BMC Biotechnology. Link

*Designed peptides as nanomolar cross-amyloid inhibitors acting via supramolecular nanofiber co-assembly. Taş K…Kapurniotu A. Nature Communications. Link

*Comparison of replicating and nonreplicating vaccines against SARS-CoV-2. Mudrick HE…Barry MA. Science Advances. Link


*Engineering null mutants in ZmFER1 confers resistance to ear rot caused by Fusarium verticillioides in maize. Liu C…Xie C. Plant Biotechnology Journal. Link

*Molecular basis of the key regulator WRINKLED1 in plant oil biosynthesis. Qiao Z…Gao Y-G. Science Advances. Link

*Nitrogenase Cofactor Maturase NifB Isolated from Transgenic Rice is Active in FeMo-co Synthesis. He W…Rubio LM. ACS Synthetic Biology. Link

*Simultaneously induced mutations in eIF4E genes by CRISPR/Cas9 enhance PVY resistance in tobacco. Le NT…Do PT. Scientific Reports. Link

Protein & Molecular Engineering

↑*Cell type-programmable genome editing with enveloped delivery vehicles. Hamilton JR…Doudna JA. bioRxiv (preprint). Link

↑*Structural plasticity enables evolution and innovation of RuBisCO assemblies. Liu AK…Shih PM. Science Advances. Link

*Engineering of NEMO as calcium indicators with ultra-high dynamics and sensitivity. Li J…Wang Y. bioRxiv (preprint). Link

*Control of protein activity by photoinduced spin polarized charge reorganization. Ghosh S…Haran G. PNAS. Link

*De novo protein design of photochemical reaction centers. Ennist NM…Moser CC. Nature Communications. Link

*A photochemically covalent lock stabilizes aptamer conformation and strengthens its performance for biomedicine. Zhou F…Zhao Z. Nucleic Acids Research. Link

*A method for targeting a specified segment of DNA to a bacterial microorganelle. Otoničar J…Butala M. Nucleic Acids Research. Link

*Directed evolution of phosphite dehydrogenase to cycle noncanonical redox cofactors via universal growth selection platform. Zhang L…Li H. Nature Communications. Link

Tools & Technology

*Directed evolution of colE1 plasmid replication compatibility: a fast tractable tunable model for investigating biological orthogonality. Chaillou S…Pinheiro VB. Nucleic Acids Research. Link

*Efficient DNA fluorescence labeling via base excision trapping. Jun Y-W…Kool ET. Nature Communications. Link

*Optogenetic Control of Bacterial Expression by Red Light. Multamäki E…Takala H. ACS Synthetic Biology. Link

*Optogenetic manipulation of cell migration with high spatiotemporal resolution using lattice lightsheet microscopy. Tang W-C…Chen B-C. Communications Biology. Link

*Fast DNA-PAINT imaging using a deep neural network. Narayanasamy KK…Heilemann M. Nature Communications. Link


*Uncovering the genomic basis of an extraordinary plant invasion. Bieker VC…Martin MD. Science Advances. Link

†Policy landscapes on human genome editing: a perspective from Latin America. Saldaña-Tejeda A…Perler L. Trends in Biotechnology. Link

*A 14,000-year-old genome sheds light on the evolution and extinction of a Pleistocene vulture. Ericson PGP…Qu Y. Communications Biology. Link

More soon,

— Niko McCarty

Twitter: @NikoMcCarty