Molecular engineering

  • 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 |

    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
  • 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
  • Letter |

    A genetically encoded fluorescent voltage indicator, SomArchon, is used to image changes in membrane voltage from many neurons simultaneously in multiple brain regions of awake, behaving mice.

    • Kiryl D. Piatkevich
    • , Seth Bensussen
    •  & Xue Han
  • Article |

    A technique for the de novo design of switchable protein systems controlled by induced conformational change is demonstrated for three functional motifs, in vitro and in yeast and mammalian cells.

    • Robert A. Langan
    • , Scott E. Boyken
    •  & David Baker
  • Article |

    An RNA-adapting CRISPR–Cas system is coupled with amplification and sequencing steps to record, retrieve and analyse changes in the transcriptome of a bacterial cell over time.

    • Florian Schmidt
    • , Mariia Y. Cherepkova
    •  & Randall J. Platt
  • Letter |

    Computationally designed icosahedral protein-based assemblies can protect their genetic material and evolve in biochemical environments, suggesting a route to the custom design of synthetic nanomaterials for non-viral drug delivery.

    • Gabriel L. Butterfield
    • , Marc J. Lajoie
    •  & David Baker
  • Letter |

    By using DNA sequence information to encode the shapes of DNA origami building blocks, shape-programmable assemblies can be created, with sizes and complexities similar to those of viruses.

    • Klaus F. Wagenbauer
    • , Christian Sigl
    •  & Hendrik Dietz
  • Letter |

    The class 2 type VI RNA-guided RNA-targeting CRISPR–Cas effector Cas13 can be engineered for RNA knockdown and binding, expanding the CRISPR toolset with a flexible platform for studying RNA in mammalian cells and therapeutic development.

    • Omar O. Abudayyeh
    • , Jonathan S. Gootenberg
    •  & Feng Zhang
  • Letter |

    CRISPR-Cas9 nucleases are widely used for genome editing, but the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM); here the commonly used Streptococcus pyogenes Cas9 (SpCas9) is modified to recognize alternative PAM sequences, enabling robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9.

    • Benjamin P. Kleinstiver
    • , Michelle S. Prew
    •  & J. Keith Joung
  • Letter |

    Triphosphates of hydrophobic nucleotides d5SICS and dNaM are imported into Escherichia coli by an exogenous algal nucleotide triphosphate transporter and then used by an endogenous polymerase to replicate, and faithfully maintain over many generations of growth, a plasmid containing the d5SICS–dNaM unnatural base pair.

    • Denis A. Malyshev
    • , Kirandeep Dhami
    •  & Floyd E. Romesberg
  • Letter |

    Synthetic analog gene circuits can be engineered to execute logarithmically linear sensing, addition, ratiometric and power-law computations in living cells using just three transcription factors.

    • Ramiz Daniel
    • , Jacob R. Rubens
    •  & Timothy K. Lu
  • Article |

    Rules that allow the design of strongly funnelled protein folding energy landscapes by relating secondary structure patterns to protein tertiary motifs are used to produce ideal protein structures stabilized by completely consistent local and non-local interactions.

    • Nobuyasu Koga
    • , Rie Tatsumi-Koga
    •  & David Baker
  • Letter |

    In a porcine cystic fibrosis model, lack of cystic fibrosis transmembrane conductance regulator (CFTR) is shown to result in acidification of airway surface liquid (ASL), and this decrease in pH reduces the ability of ASL to kill bacteria; the findings directly link loss of the CFTR anion channel to impaired defence against bacterial infection.

    • Alejandro A. Pezzulo
    • , Xiao Xiao Tang
    •  & Joseph Zabner
  • Letter |

    In synthetic biology, the use of regulatory proteins that bind either DNA or RNA to reprogram mammalian cellular functions allows a variety of computational ‘logic circuits’ to be built in a plug-and-play manner, which may pave the way for precise and robust control of future gene-based and cell-based therapies.

    • Simon Ausländer
    • , David Ausländer
    •  & Martin Fussenegger
  • Article |

    Thousands of quorum-sensing Escherichia coli colonies are synchronized over centimetres using redox signalling to create ‘biopixels’ that can sense trace amounts of arsenic in water.

    • Arthur Prindle
    • , Phillip Samayoa
    •  & Jeff Hasty