• Article
    | Open Access

    Membrane-bound E3 ubiquitin ligases RNF43 and ZNRF3 are overexpressed in colorectal cancer, and can be repurposed using proteolysis-targeting antibodies (PROTABs) to selectively degrade cell-surface receptors in tumours.

    • Hadir Marei
    • , Wen-Ting K. Tsai
    •  & Felipe de Sousa e Melo
  • Article |

    A bacteriogenic strategy for constructing membrane-bounded, molecularly crowded, and compositionally, structurally and morphologically complex synthetic cells provides opportunities for the fabrication of new synthetic cell modules and augmented living/synthetic cell constructs.

    • Can Xu
    • , Nicolas Martin
    •  & Stephen Mann
  • Article
    | Open Access

    De novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast and in vitro chemical coupling to vinblastine is carried out, positioning yeast as a scalable platform to produce many monoterpene indole alkaloids.

    • Jie Zhang
    • , Lea G. Hansen
    •  & Jay D. Keasling
  • Article
    | Open Access

    Live-seq, a single-cell transcriptome profiling approach that preserves cell viability during RNA extraction using fluidic force microscopy, can address a range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.

    • Wanze Chen
    • , Orane Guillaume-Gentil
    •  & Bart Deplancke
  • Article |

    Untreated, postconsumer-PET from 51 different thermoformed products can all be almost completely degraded by FAST-PETase in 1 week and PET can be resynthesized from the recovered monomers, demonstrating recycling at the industrial scale.

    • Hongyuan Lu
    • , Daniel J. Diaz
    •  & Hal S. Alper
  • Article |

    The feasibility of adeno-associated-virus-delivered nonsense suppressor tRNAs operating on premature termination codons (AAV-NoSTOP) is explored to restore gene function, using a mouse model of mucopolysaccharidosis type I for proof of concept.

    • Jiaming Wang
    • , Yue Zhang
    •  & Dan Wang
  • Article |

    A genome-scale gain-of-function screen using overexpression of nearly 12,000 open reading frames (ORFs) identifies positive regulators of human T cell function and suggests that ORF-based screens could be applied clinically to improve T cell therapies.

    • Mateusz Legut
    • , Zoran Gajic
    •  & Neville E. Sanjana
  • Article
    | Open Access

    Analyses of circulating cell-free RNA (cfRNA) in blood samples from pregnant mothers identify changes in gene expression that could be used in liquid biopsy tests to identify and monitor individuals who are at risk of preeclampsia.

    • Mira N. Moufarrej
    • , Sevahn K. Vorperian
    •  & Stephen R. Quake
  • Article |

    Tamlo-R32, an engineered wheat mutant allele of the Mildew resistance locus O (MLO) gene, confers resistance to powdery mildew, retains robust wheat growth, and can be transferred to other agriculturally important wheat varieties.

    • Shengnan Li
    • , Dexing Lin
    •  & Caixia Gao
  • Article
    | Open Access

    A comprehensive survey of the epigenome from 45 regions of the mouse cortex, hippocampus, striatum, pallidum and olfactory areas using single-nucleus DNA methylation sequencing enables identification of 161 cell clusters with distinct locations and projection targets and provides insights into the regulatory landscape underlying neuronal diversity and spatial regulation.

    • Hanqing Liu
    • , Jingtian Zhou
    •  & Joseph R. Ecker
  • Article |

    Cas7-11—the fusion of a putative Cas11 domain and four Cas7 subunits—cleaves RNA without detectable non-specific activity and, when optimized for RNA knockdown and editing in mammalian cells, has no effects on cell viability.

    • Ahsen Özcan
    • , Rohan Krajeski
    •  & Jonathan S. Gootenberg
  • Article |

    A switch system is developed to control the expression of therapeutic genes, involving the administration of a small-molecule drug to induce splicing-mediated control of mRNA translation.

    • Alex Mas Monteys
    • , Amiel A. Hundley
    •  & Beverly L. Davidson
  • Article |

    In a cynomolgus macaque model, CRISPR base editors delivered in lipid nanoparticles are shown to efficiently and stably knock down PCSK9 in the liver to reduce levels of PCSK9 and low-density lipoprotein cholesterol in the blood.

    • Kiran Musunuru
    • , Alexandra C. Chadwick
    •  & Sekar Kathiresan
  • Article |

    Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.

    • Eric Y. Wang
    • , Tianyang Mao
    •  & Aaron M. Ring
  • Perspective
    | Open Access

    This Perspective discusses how the Somatic Cell Genome Editing Consortium aims to accelerate the implementation of safe and effective genome-editing therapies in the clinic.

    • Krishanu Saha
    • , Erik J. Sontheimer
    •  & Jiangbing Zhou
  • Article |

    The bispecific IgG1-like CoV-X2 prevents SARS-CoV-2 spike binding to ACE2, neutralizes SARS-CoV-2 and its variants of concern, protects against disease in a mouse model, whereas the parental monoclonal antibodies generate viral escape.

    • Raoul De Gasparo
    • , Mattia Pedotti
    •  & Luca Varani
  • Article |

    A modular de novo designed biosensor platform consisting of a cage and key molecule is developed, and used to create sensors for seven distinct proteins including the spike protein from SARS-CoV-2 and anti-SARS antibodies.

    • Alfredo Quijano-Rubio
    • , Hsien-Wei Yeh
    •  & David Baker
  • Article |

    Lateral-flow in vitro diagnostic assays based on fluorescent nanodiamonds, in which microwave-based spin manipulation is used to increase sensitivity, are demonstrated using the biotin–avidin model and by the single-copy detection of HIV-1 RNA.

    • Benjamin S. Miller
    • , Léonard Bezinge
    •  & Rachel A. McKendry
  • Article |

    A robotic pipeline is used to survey a library of mutations in a Drosphila gene enhancer, showing that most mutations altered gene expression and had widespread pleiotropic effects that are likely to constrain regulatory evolution.

    • Timothy Fuqua
    • , Jeff Jordan
    •  & Justin Crocker
  • Article |

    The alkaloid drugs hyoscyamine and scopolamine are synthesized from sugars and amino acids in yeast, using 26 genes from yeast, plants, bacteria and animals, protein engineering and a vacuole transporter to enable functional expression of a key acyltransferase.

    • Prashanth Srinivasan
    •  & Christina D. Smolke
  • Article |

    An approach for the design of protein pores is demonstrated by the computational design and subsequent experimental expression of both an ion-selective and a large transmembrane pore.

    • Chunfu Xu
    • , Peilong Lu
    •  & David Baker
  • Article |

    An advanced proteomics workflow is used to identify 340,000 proteins from 100 taxonomically diverse species, providing a comparative view of proteomes across the evolutionary range.

    • Johannes B. Müller
    • , Philipp E. Geyer
    •  & Matthias Mann
  • Article |

    Skin organoids generated in vitro from human pluripotent stem cells form complex, multilayered skin tissue with hair follicles, sebaceous glands and neural circuitry, and integrate with endogenous skin when grafted onto immunocompromised mice.

    • Jiyoon Lee
    • , Cyrus C. Rabbani
    •  & Karl R. Koehler
  • Article |

    SARS-CoV-2 modulates central cellular pathways, such as translation, splicing, carbon metabolism, proteostasis and nucleic acid metabolism, in human cells; these pathways can be inhibited by small-molecule inhibitors to prevent viral replication in the cells.

    • Denisa Bojkova
    • , Kevin Klann
    •  & Christian Münch
  • Article
    | Open Access

    CRISPR-based nucleic acid detection is used in a platform that can simultaneously detect 169 human-associated viruses in multiple samples, providing scalable, multiplexed pathogen detection aimed at routine surveillance for public health.

    • Cheri M. Ackerman
    • , Cameron Myhrvold
    •  & Pardis C. Sabeti
  • Review Article |

    The development and future prospects of prospectively designed multispecific drugs, which have the potential to transform the biopharmaceutical industry by enabling the targeting of currently inaccessible components of the proteome, are reviewed.

    • Raymond J. Deshaies
  • Article |

    Computer-aided engineering produces improvements to an enzyme that breaks down poly(ethylene terephthalate) (PET) into its constituent monomers, which are used to synthesize PET of near-petrochemical grade that can be further processed into bottles.

    • V. Tournier
    • , C. M. Topham
    •  & A. Marty
  • Article |

    Single-cell RNA sequencing is used to generate a dataset covering all major human organs in both adult and fetal stages, enabling comparison with similar datasets for mouse tissues.

    • Xiaoping Han
    • , Ziming Zhou
    •  & Guoji Guo
  • Article |

    Single-cell mapping of chromatin accessibility, DNA methylation and RNA expression during gastrulation in mouse embryos shows characteristic epigenetic changes that accompany formation of the primary germ layers.

    • Ricard Argelaguet
    • , Stephen J. Clark
    •  & Wolf Reik
  • Article |

    Compounds that interact with mutant huntingtin and an autophagosomal protein are able to reduce cellular levels of mutant huntingtin by targeting it for autophagic degradation, demonstrating an approach that may have potential for treating proteopathies.

    • Zhaoyang Li
    • , Cen Wang
    •  & Boxun Lu