Prime-Edited Labrador Retrievers

Prime editing has also made its way into dogs. A Korean team used the technology to correct a genetic mutation related to canine hip dysplasia in two Labrador retrievers.

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I’m writing this newsletter from Acadia National Park. Or, specifically, I’m sitting in an 1840s-era hotel with garish, floral, Victorian wallpaper. There are strange paintings in my room of children wearing old-fashioned gowns with those white, frilly things around the collars. The window curtains are made of white lace. The walls are thin. My keyboard rattles. Boo.

A biological device, called Retro-Cascorder, can log the specific order in which genes turn on, inside of single cells. The paper was published in Nature, and I wrote about it here. That’s the big paper this week.

But I’d be a poor writer (no jokes plz) if I didn’t mention the AlphaFold announcement, too. Over 200 million protein structure predictions are now available online. Browse the full collection here. On a related note, a new language model called ProtGTP2 can generate de novo protein design predictions “in a matter of seconds,” and is freely available to Pythonistas.

Prime editing has also made its way into dogs. A Korean team used the technology to correct a genetic mutation related to canine hip dysplasia in two Labrador retrievers. The paper is not very good, or exhaustive, but the idea is captivating: Will rich people start paying genetic engineers to cure their beloved poodle of disease? I’m reminded of cloning and Barbra Streisand.

Lastly, my favorite paper of the week: A nano-winch built using DNA origami. This little device can open individual protein channels, on the membranes of living cells, with piconewton-level force; its actuation strength is controlled by single- or double-stranded DNA inputs. In the study, the nano-winch was used to open a force-responsive gated channel, called BtuB, to study mechanotransduction pathways in living cells. Amazing.

All of these recommended papers, and more, are marked with the ↑ symbol. Happy link-clicking!

The Bio(tech) Index

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

Basic Research

↑Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics. Keizer VI…Coulon A. Science. Link

*Natural Evolution Provides Strong Hints about Laboratory Evolution of Designer Enzymes. Xie WJ & Warshel A. PNAS. Link

*Uncovering translation roadblocks during the development of a synthetic tRNA. Prabhakar A…Puglisi J. Nucleic Acids Research. Link

*Pathogenic bacteria remodel central metabolic enzyme to build a cyclopropanol warhead. Trottmann F…Hertweck C. Nature Chemistry. Link

Prebiotic synthesis of α-amino acids and orotate from α-ketoacids potentiates transition to extant metabolic pathways. Pulletikurti S…Krishnamurthy R. Nature Chemistry. Link

*Global analysis of cytosine and adenine DNA modifications across the tree of life. Varma SJ…Ralser M. eLife. Link

Biomanufacturing & Metabolic Engineering

*Expanding the genetic engineering toolbox for the metabolically flexible acetogen Eubacterium limosum. Sanford PA & Woolston BM. Journal of Industrial Microbiology and Biotechnology. Link

†Building biomaterials through genetic code expansion. Sisila V…Ayyadurai N. Trends in Biotechnology. Link

*Systems metabolic engineering of Corynebacterium glutamicum eliminates all by-products for selective and high-yield production of the platform chemical 5-aminovalerate. Rohles C…Wittmann C. Metabolic Engineering. Link

*†Biotechnological application of Streptomyces for the production of clinical drugs and other bioactive molecules. Del Carratore F…Takano E. Current Opinion in Biotechnology. Link

†Delineating biosynthesis of Huperzine A, A plant-derived medicine for the treatment of Alzheimer's disease. Li X…Tan T. Biotechnology Advances. Link


In vivo protein-based biosensors: seeing metabolism in real time. Alexandrov K & Vickers CE. Trends in Biotechnology. Link


*Cascaded dissipative DNAzyme-driven layered networks guide transient replication of coded-strands as gene models. Wang J, Li Z & Willner I. Nature Communications. Link

*DNA circuits compatible encoder and demultiplexer based on a single biomolecular platform with DNA strands as outputs. Xie T…Wu T. Nucleic Acids Research. Link

Computational Tools & Models

*Self-supervised deep learning encodes high-resolution features of protein subcellular localization. Kobayashi H…Royer LA. Nature Medicine. Link

↑*ProtGPT2 is a deep unsupervised language model for protein design. Ferruz N, Schmidt S & Höcker B. Nature Communications. Link

*Frequency spectra and the color of cellular noise. Gupta A & Khammash M. Nature Communications. Link

*Integrating knowledge and omics to decipher mechanisms via large-scale models of signaling networks. Garrido-Rodriguez M…Saez-Rodriguez J. Molecular Systems Biology. Link

*The role of division stochasticity on the robustness of bacterial size dynamics. Nieto C…Pedraza JM. bioRxiv (preprint). Link

CRISPR & Gene Editing

↑*Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors. Davis JR…Liu DR. Nature Biomedical Engineering. Link

*Multi-step screening of DNA/lipid nanoparticles and co-delivery with siRNA to enhance and prolong gene expression. Zhu Y…Mao H-Q. Nature Communications. Link

†CRISPR-Cas12c: a noncleaving DNA binder with minimal PAM requirement. Awan MJA, Amin I & Mansoor S. Trends in Biotechnology. Link

*Reduced gene templates for supervised analysis of scale-limited CRISPR-Cas9 fitness screens. Vinceti A…Iorio F. Cell Reports. Link

*Biallelic and gene-wide genomic substitution for endogenous intron and retroelement mutagenesis in human cells. Ohno T…Aizawa Y. Nature Communications. Link

Medicine & Diagnostics

*Uncovering the mode of action of engineered T cells in patient cancer organoids. Dekkers JF…Rios AC. Nature Biotechnology. Link

*A lentiviral vector encoding fusion of light invariant chain and mycobacterial antigens induces protective CD4+ T cell immunity. Lopez J…Majlessi L. Cell Reports. Link

*Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection. Cui Z…Wang Q. Nature Chemical Biology. Link

↑*Prime editor-mediated correction of a pathogenic mutation in purebred dogs. Kim DE…Kim MK. Scientific Reports. Link


↑*Building artificial plant cell wall on lipid bilayer by assembling polysaccharides and engineered proteins. Notova S…Imberty A. bioRxiv (preprint). Link

*Building the Plant SynBio Toolbox through Combinatorial Analysis of DNA Regulatory Elements. Pfotenhauer AC…Lenaghan SC. ACS Synthetic Biology. Link

*The Gardenia Carotenoid Cleavage Dioxygenase 4a is an efficient tool for biotechnological production of crocins in green and non-green plant tissues. Zheng X…Al-Babili S. Plant Biotechnology Journal. Link

*Provoking a silent R gene in wheat genome confers resistance to powdery mildew. Li M…Liu Z. Plant Biotechnology Journal. Link

Rapid and cloning-free screening of edited alfalfa via next-generation sequencing. Stritzler M…Soto G. Plant Cell, Tissue and Organ Culture. Link

Protein & Molecular Engineering

Directed evolution of adeno-associated virus for efficient gene delivery to microglia. Lin R…Luo M. Nature Methods. Link

*Nanocarriers based on bacterial membrane materials for cancer vaccine delivery. Zhao X, Zhao R & Nie G. Nature Protocols. Link

*Structure-guided and phage-assisted evolution of a therapeutic anti-EGFR antibody to reverse acquired resistance. Zhuang X…Pan L. Nature Communications. Link

Rapid Assembly and Prototyping of Biocatalytic Virus-like Particle Nanoreactors. Esquirol L…Sainsbury F. ACS Synthetic Biology. Link

Synthetic Cells

↑*A gene expression control technology for cell-free systems and synthetic cells via targeted gene silencing and transfection. Sato W…Adamala KP. bioRxiv (preprint). Link

*Engineering cellular communication between light-activated synthetic cells and bacteria. Smith JM, Hartmann D & Booth MJ. bioRxiv (preprint). Link

†Hydrogels as functional components in artificial cell systems. Allen ME…Elani Y. Nature Reviews Chemistry. Link

Tools & Technology

↑Recording gene expression order in DNA by CRISPR addition of retron barcodes. Bhattarai-Kline S…Shipman SL. Nature. Link (My coverage in Codon).

↑*A modular spring-loaded actuator for mechanical activation of membrane proteins. Mills A…Bellot G. Nature Communications. Link

A rapid screening platform to coculture bacteria within tumor spheroids. Harimoto T, Deb D & Danino T. Nature Protocols. Link

*See-N-Seq: RNA sequencing of target single cells identified by microscopy via micropatterning of hydrogel porosity. Lee JH…Ma H. Communications Biology. Link

*Defunctionalizing intracellular organelles such as mitochondria and peroxisomes with engineered phospholipase A/acyltransferases. Watanabe S…Inoue T. Nature Communications. Link


↑Why it is important to study human–monkey embryonic chimeras in a dish. De Los Angeles A…Zambidis ET. Nature Methods. Link

*Multicolor Plate Reader Fluorescence Calibration. Beal J…Traci Haddock-Angelli. Synthetic Biology. Link

*Ancient Yersinia pestis and Salmonella enterica genomes from Bronze Age Crete. Neumann GU…Stockhammer PW. Current Biology. Link

*Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia. Guellil M…Scheib CL. Science Advances. Link

†Ethical aspects of GMO regulation in the EU. Ramsay T…Emerson C. EMBO Reports. Link

†Preparing for future challenges in risk assessment in the European Union. Garcia-Vello P…Heppner C. Trends in Biotechnology. Link

More soon,

— Niko McCarty

Twitter: @NikoMcCarty