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Global health equity: the next waiver
doi : 10.1038/s41587-022-01623-5
Volume 40 Issue 12, December 2022
TYK2-blocking agent showcases power of atypical kinase
Elie DolginÂÂ
Noma: from grasshopper brews to age-old ‘garum’
Lisa MeltonÂÂ
Parkinson’s disease drug hunters think outside the α-synuclein box
Ben JohnsonÂ
Innovating manufacturing technology in emerging economies
Anurag Rathore & Faheem ShereefÂ
Long-term preservation of liver grafts brings ‘off-the-shelf’ organs closer
Paulo N. Martins & Davide GhinolfiÂ
Improving combination drug trials using ‘definitive screening designs’
Michael Dodds, James Roberts & Brian FinrowÂ
The Humira patent thicket, the Noerr–Pennington doctrine and antitrust’s patent problem
Ryan Knox & Gregory CurfmanÂ
Single-molecule peptide sequencing on semiconductor chips
Grant OttoÂÂ
Profiling the total single-cell transciptome using droplet microfluidics
Wastewater is a robust proxy for monitoring circulating SARS-CoV-2 variants
Identifying drug combinations that enhance treatment responses mediated by the tumor microenvironment
Enhancing untargeted metabolomics using metadata-based source annotation
Julia M. Gauglitz, Kiana A. West, Wout Bittremieux, Candace L. Williams, Kelly C. Weldon, Morgan Panitchpakdi, Francesca Di Ottavio, Christine M. Aceves, Elizabeth Brown, Nicole C. Sikora, Alan K. Jarmusch, Cameron Martino, Anupriya Tripathi, Michael J. Meehan, Kathleen Dorrestein, Justin P. Shaffer, Roxana Coras, Fernando Vargas, Lindsay DeRight Goldasich, Tara Schwartz, MacKenzie Bryant, Gregory Humphrey, Abigail J. Johnson, Katharina Spengler, …Pieter C. DorresteinÂ
doi : 10.1038/s41587-022-01368-1
Human untargeted metabolomics studies annotate only ~10% of molecular features. We introduce reference-data-driven analysis to match metabolomics tandem mass spectrometry (MS/MS) data against metadata-annotated source data as a pseudo-MS/MS reference library.
High-throughput total RNA sequencing in single cells using VASA-seq
Fredrik Salmen, Joachim De Jonghe, Tomasz S. Kaminski, Anna Alemany, Guillermo E. Parada, Joe Verity-Legg, Ayaka Yanagida, Timo N. Kohler, Nicholas Battich, Floris van den Brekel, Anna L. Ellermann, Alfonso Martinez Arias, Jennifer Nichols, Martin Hemberg, Florian Hollfelder & Alexander van OudenaardenÂ
doi : 10.1038/s41587-022-01361-8
Most methods for single-cell transcriptome sequencing amplify the termini of polyadenylated transcripts, capturing only a small fraction of the total cellular transcriptome. This precludes the detection of many long non-coding, short non-coding and non-polyadenylated protein-coding transcripts and hinders alternative splicing analysis.
High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging
Shanshan He, Ruchir Bhatt, Carl Brown, Emily A. Brown, Derek L. Buhr, Kan Chantranuvatana, Patrick Danaher, Dwayne Dunaway, Ryan G. Garrison, Gary Geiss, Mark T. Gregory, Margaret L. Hoang, Rustem Khafizov, Emily E. Killingbeck, Dae Kim, Tae Kyung Kim, Youngmi Kim, Andrew Klock, Mithra Korukonda, Alecksandr Kutchma, Zachary R. Lewis, Yan Liang, Jeffrey S. Nelson, Giang T. Ong, …Joseph M. BeechemÂ
doi : 10.1038/s41587-022-01483-z
Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology.
Frequent aneuploidy in primary human T cells after CRISPR–Cas9 cleavage
Alessio David Nahmad, Eli Reuveni, Ella Goldschmidt, Tamar Tenne, Meytal Liberman, Miriam Horovitz-Fried, Rami Khosravi, Hila Kobo, Eyal Reinstein, Asaf Madi, Uri Ben-David & Adi BarzelÂ
doi : 10.1038/s41587-022-01377-0
Multiple clinical trials of allogeneic T cell therapy use site-specific nucleases to disrupt T cell receptor (TCR) and other genes1,2,3,4,5,6. In this study, using single-cell RNA sequencing, we investigated genome editing outcomes in primary human T cells transfected with CRISPR–Cas9 and guide RNAs targeting genes for TCR chains and programmed cell death protein 1.
Viral variant-resolved wastewater surveillance of SARS-CoV-2 at national scale
Fabian Amman, Rudolf Markt, Lukas Endler, Sebastian Hupfauf, Benedikt Agerer, Anna Schedl, Lukas Richter, Melanie Zechmeister, Martin Bicher, Georg Heiler, Petr Triska, Matthew Thornton, Thomas Penz, Martin Senekowitsch, Jan Laine, Zsofia Keszei, Peter Klimek, Fabiana Nägele, Markus Mayr, Beatrice Daleiden, Martin Steinlechner, Harald Niederstätter, Petra Heidinger, Wolfgang Rauch, …Andreas BergthalerÂ
doi : 10.1038/s41587-022-01387-y
SARS-CoV-2 surveillance by wastewater-based epidemiology is poised to provide a complementary approach to sequencing individual cases. However, robust quantification of variants and de novo detection of emerging variants remains challenging for existing strategies.
A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs
Zuzana Tatarova, Dylan C. Blumberg, James E. Korkola, Laura M. Heiser, John L. Muschler, Pepper J. Schedin, Sebastian W. Ahn, Gordon B. Mills, Lisa M. Coussens, Oliver Jonas & Joe W. GrayÂ
doi : 10.1038/s41587-022-01379-y
Systematically identifying synergistic combinations of targeted agents and immunotherapies for cancer treatments remains difficult.
Ras-mutant cancers are sensitive to small molecule inhibition of V-type ATPases in mice
Bhairavi Tolani, Anna Celli, Yanmin Yao, Yong Zi Tan, Richard Fetter, Christina R. Liem, Adam J. de Smith, Thamiya Vasanthakumar, Paola Bisignano, Adam D. Cotton, Ian B. Seiple, John L. Rubinstein, Marco Jost & Jonathan S. WeissmanÂ
doi : 10.1038/s41587-022-01386-z
Mutations in Ras family proteins are implicated in 33% of human cancers, but direct pharmacological inhibition of Ras mutants remains challenging. As an alternative to direct inhibition, we screened for sensitivities in Ras-mutant cells and discovered 249C as a Ras-mutant selective cytotoxic agent with nanomolar potency against a spectrum of Ras-mutant cancers.
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants
Sylvia Rothenberger, Daniel L. Hurdiss, Marcel Walser, Francesca Malvezzi, Jennifer Mayor, Sarah Ryter, Hector Moreno, Nicole Liechti, Andreas Bosshart, Chloé Iss, Valérie Calabro, Andreas Cornelius, Tanja Hospodarsch, Alexandra Neculcea, Thamar Looser, Anja Schlegel, Simon Fontaine, Denis Villemagne, Maria Paladino, Dieter Schiegg, Susanne Mangold, Christian Reichen, Filip Radom, Yvonne Kaufmann, …Jakob TrimpertÂ
doi : 10.1038/s41587-022-01382-3
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity.
Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds
Jesús Beltrán, Paul J. Steiner, Matthew Bedewitz, Shuang Wei, Francis C. Peterson, Zongbo Li, Brigid E. Hughes, Zachary Hartley, Nicholas R. Robertson, Angélica V. Medina-Cucurella, Zachary T. Baumer, Alison C. Leonard, Sang-Youl Park, Brian F. Volkman, Dmitri A. Nusinow, Wenwan Zhong, Ian Wheeldon, Sean R. Cutler & Timothy A. WhiteheadÂ
doi : 10.1038/s41587-022-01364-5
A general method to generate biosensors for user-defined molecules could provide detection tools for a wide range of biological applications. Here, we describe an approach for the rapid engineering of biosensors using PYR1 (Pyrabactin Resistance 1), a plant abscisic acid (ABA) receptor with a malleable ligand-binding pocket and a requirement for ligand-induced heterodimerization, which facilitates the construction of sense–response functions.
Synthetic memory circuits for stable cell reprogramming in plants
James P. B. Lloyd, Florence Ly, Patrick Gong, Jahnvi Pflueger, Tessa Swain, Christian Pflueger, Elliott Fourie, Muhammad Adil Khan, Brendan N. Kidd & Ryan ListerÂ
doi : 10.1038/s41587-022-01383-2
Plant biotechnology predominantly relies on a restricted set of genetic parts with limited capability to customize spatiotemporal and conditional expression patterns. Synthetic gene circuits have the potential to integrate multiple customizable input signals through a processing unit constructed from biological parts to produce a predictable and programmable output.
Author Correction: Engineering the amoeba Dictyostelium discoideum for biosynthesis of a cannabinoid precursor and other polyketides
Christin Reimer, Johann E. Kufs, Julia Rautschek, Lars Regestein, Vito Valiante & Falk HillmannÂ
How to grow (almost) anything: a hybrid distance learning model for global laboratory-based synthetic biology education
Eyal Perry, Jessica Weber, Pat Pataranutaporn, Verena Volf, Laura Maria Gonzalez, Sara Nejad, Carolyn Angleton, Jia-En Chen, Ananda Gabo, Mani Sai Suryateja Jammalamadaka, Erkin Kuru, Patrick Fortuna, Andres Rico, Karolina Sulich, Dominika Wawrzyniak, Joseph Jacobson, George Church & David KongÂ
