Biotechnology articles within Nature Communications

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  • Article
    | Open Access

    Intrinsic and acquired resistances to CDK4/6 inhibitors have been described in patients with breast cancer. Here the authors report the results from a phase I/II clinical trial of the aromatase inhibitor exemestane plus everolimus (mTOR inhibitor) and palbociclib (CDK4/6i) in patients with metastatic breast cancer, assessing safety, clinical efficacy, as well as genomic and transcriptomic determinants of resistance.

    • Jorge Gómez Tejeda Zañudo
    • , Romualdo Barroso-Sousa
    •  & Nikhil Wagle
  • Article
    | Open Access

    The unification of decision-making, communication, and memory would enable the programming of intelligent biotic systems. Here, the authors achieve this goal by engineering E. coli chassis cells with an array of inducible recombinases that mediate diverse genetic programs.

    • Brian D. Huang
    • , Dowan Kim
    •  & Corey J. Wilson
  • Article
    | Open Access

    Bispecific antibody architecture is often important for function but rarely optimized. Here, authors present a modular approach to assemble bispecifics in varied formats using a SpyTag/SpyCatcher approach called SpyMask, and build anti-HER2 bispecifics whose activities depend on binder orientation and bispecific geometry.

    • Claudia L. Driscoll
    • , Anthony H. Keeble
    •  & Mark R. Howarth
  • Article
    | Open Access

    Alternatively activated macrophages have a pivotal role in resolving inflammation but in the tumour microenvironment they are immunosuppressive. Here author show that adoptively transferred engineered macrophages harbouring a heat-inducible genetic switch can resist the polarizing effect of the tumour microenvironment, and do not only remain pro-inflammatory themselves but also re-polarise the endogenous macrophages upon controlled warming with a purpose-made device.

    • Yanan Xue
    • , Xiaojie Yan
    •  & Yuan Ping
  • Article
    | Open Access

    Targeting the files containing content-of-interest is a challenge in DNA data storage. Here, the authors develop a CRISPR-powered search engine to quantitatively identify the keyword in files stored in DNA.

    • Jiongyu Zhang
    • , Chengyu Hou
    •  & Changchun Liu
  • Article
    | Open Access

    While tricarboxylic acid cycle (TCA cycle) is required for heterotrophic microbes, it reduces carbon yield of industrial products due to the release of excess CO2. Here, the authors construct an E. coli strain without a functional TCA cycle and demonstrate its feasibility as a chassis strain for production of four separate compounds.

    • Hang Zhou
    • , Yiwen Zhang
    •  & Baixue Lin
  • Article
    | Open Access

    Machine learning applied to large compendia of transcriptomic data has enabled the decomposition of bacterial transcriptomes to identify independently modulated sets of genes. Here the authors present iModulon-based engineering for precise identification of genes for cross-species function transfer to streamline synthetic biology for strain development and biomanufacturing.

    • Donghui Choe
    • , Connor A. Olson
    •  & Bernhard O. Palsson
  • Article
    | Open Access

    Fungi have the potential to produce sustainable foods for a growing population, but current products are based on a small number of strains with inherent limitations. Here, the authors develop genetic tools for an edible fungus and engineer its nutritional value and sensory appeal for alternative meat applications.

    • Vayu Maini Rekdal
    • , Casper R. B. van der Luijt
    •  & Jay D. Keasling
  • Article
    | Open Access

    Developing clinically predictive model systems for evaluating gene transfer and gene editing technologies has become increasingly important. This study introduces human liver ex situ normothermic perfusion as a model to evaluate gene therapy vectors, paving the way for advanced liver disease treatment.

    • Marti Cabanes-Creus
    • , Sophia H. Y. Liao
    •  & Leszek Lisowski
  • Article
    | Open Access

    The ability to edit large stretches of mRNA transcripts remains a significant challenge. Here, the authors demonstrate that CRISPR-Cas13 systems can be repurposed to assist trans-splicing of exogenous RNA fragments into an endogenous pre-mRNA transcript, a method termed CRISPR Assisted mRNA Fragment Trans-splicing (CRAFT).

    • David N. Fiflis
    • , Nicolas A. Rey
    •  & Aravind Asokan
  • Article
    | Open Access

    When stem cells develop into tissues intracellular signalling is rewired, errors in this process lead to cancer. Here, authors applied tools from differential geometry made by Albert Einstein’s General Relativity to understand and predict biological network rewiring in health and disease.

    • Anthony Baptista
    • , Ben D. MacArthur
    •  & Christopher R. S. Banerji
  • Article
    | Open Access

    Bacteriophages have great potential in both medicine and biotechnology. Here the authors present PHEIGES, a cell-free method for phage genome engineering, synthesis and selection based on T7, which allows direct selection of engineered and mutant phages without compartmentalization.

    • Antoine Levrier
    • , Ioannis Karpathakis
    •  & Vincent Noireaux
  • Article
    | Open Access

    Inhibiting SARS-CoV-2 interaction with ACE2 is a promising antiviral strategy. Here, the authors show that exosomes derived from human lung spheroid cells expressing hACE2 accumulate in the lung following prophylactic inhalation to bind and neutralize SARS-CoV-2 and protect mice from SARS-CoV-2-induced disease.

    • Zhenzhen Wang
    • , Shiqi Hu
    •  & Ke Cheng
  • Article
    | Open Access

    Binning is an essential step in genome-resolved metagenomic analysis in which assembled contigs originating from the same source population are clustered. However it is challenging, especially for low abundance microbial species. Here the authors introduce a toolkit that integrates multiple prominent binning tools and AI for efficient and high-resolution recovery of non-redundant bins from short- and long-read metagenomic sequencing datasets.

    • Zhiguang Qiu
    • , Li Yuan
    •  & Ke Yu
  • Article
    | Open Access

    Current gene silencing tools can have drawbacks. Here the authors report CRISPRδ, an approach for translational silencing, harnessing catalytically inactive Cas13 proteins (dCas13): they also show that fusion of a translational repressor to dCas13 further improved the performance.

    • Antonios Apostolopoulos
    • , Naohiro Kawamoto
    •  & Shintaro Iwasaki
  • Article
    | Open Access

    The delivery of therapeutic payloads and living vectors to tumors remains a clinical challenge. Here the authors explore a spatially targeted control strategy applying torque density to magnetotactic bacteria, demonstrating feasibility in vitro and in vivo.

    • Nima Mirkhani
    • , Michael G. Christiansen
    •  & Simone Schuerle
  • Article
    | Open Access

    Activatable afterglow luminescence nanoprobes reduce unspecific signals and improve imaging fidelity, but their utility is limited by a requisition of donor-acceptor distance (>10 nm) in common biomarker-activatable designs. Here, the authors address this issue by developing organic afterglow luminescence cocktail nanoparticles for acid-activatable upconversion afterglow luminescence imaging.

    • Yue Jiang
    • , Min Zhao
    •  & Qingqing Miao
  • Article
    | Open Access

    Compared to traditional Cas9 nucleases prime editors (PEs) are less active. Here the authors use OrthoRep, a yeast-based platform for directed protein evolution to enhance the editing efficiency of PEs: they identify mutations that have a positive effect on kinetics and use this knowledge to generate an efficient in vivo PE.

    • Yanik Weber
    • , Desirée Böck
    •  & Gerald Schwank
  • Article
    | Open Access

    Engineered biosensing bacteria can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. Here the authors present a robust biocontainment assisted by Cas9 and an engineered gene expression control combined in a genetically engineered human commensal bacterium that successfully functioned in a mouse intestinal tract as well as cell culture condition.

    • Naoki Hayashi
    • , Yong Lai
    •  & Timothy K. Lu
  • Article
    | Open Access

    Amaryllidaceae alkaloids, such as the Alzheimer’s medication galantamine, are currently extracted from low-yielding daffodils. Here, authors pair biosensor-assisted screening with machine learning-guided protein design to rapidly engineer an improved Amaryllidaceae enzyme in a microbial host.

    • Simon d’Oelsnitz
    • , Daniel J. Diaz
    •  & Andrew D. Ellington
  • Article
    | Open Access

    Bioresorbable neural implants offer a promising solution to the challenges of secondary surgeries required for the removal of implanted devices. Here, the authors introduce a fully bioresorbable flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optogenetic stimulation.

    • Myeongki Cho
    • , Jeong-Kyu Han
    •  & Ki Jun Yu
  • Article
    | Open Access

    Rational antibody engineering can greatly improve the clinical value of therapeutic antibodies. Here authors describe ISB 1442, a fully human bispecific antibody, consisting of two targeting modules against two different epitopes on CD38, combined with a targeting module blocking CD47 and engineered effector properties, to enhance complement dependent cytotoxicity, antibody dependent cells cytotoxicity and antibody dependent cell phagocytosis to combat multiple myeloma.

    • C. Grandclément
    • , C. Estoppey
    •  & S. Sammicheli
  • Article
    | Open Access

    Fruits contain a large variety of cis-diols but their rapid and direct analysis without complex sample pretreatment was not achieved. Here, the authors report a Mycobacterium smegmatis porin A nanopore modified with a phenylboronic acid adapter for recognition of 1,2-diphenols, alditols, α-hydroxy acids and saccharides in fruits.

    • Pingping Fan
    • , Zhenyuan Cao
    •  & Shuo Huang
  • Article
    | Open Access

    All natural AAV serotypes transduce murine hepatocytes more efficiently than their human counterparts in human liver chimeric mouse models. Here the authors developed a novel humanized mouse were human transduction of AAV can be studied.

    • Mercedes Barzi
    • , Tong Chen
    •  & Karl-Dimiter Bissig
  • Article
    | Open Access

    Artificial biomolecular condensates are valuable tools to study the design principles of phase separation. Here, the authors demonstrate and characterize a model system of artificial DNA condensates whose kinetic formation and dissolution depends on DNA inputs that activate or deactivate the phase separating DNA subunits.

    • Siddharth Agarwal
    • , Dino Osmanovic
    •  & Elisa Franco
  • Article
    | Open Access

    Winged bean is a tropical legume that can produce similar level of seed protein to soybean. Here, the authors report the genome assembly, population genetics, QTL mapping of the plant architecture, protein content and phytonutrients for this species.

    • Wai Kuan Ho
    • , Alberto Stefano Tanzi
    •  & Sean Mayes
  • Article
    | Open Access

    Identifying pulmonary delivery of lipid libraries poses an obstacle for mRNA drugs. Here, the authors use a barcoded screening system to identify lung-targeting of cationic, degradable lipid-like materials for mRNA delivery and gene editing in female preclinical models.

    • Lulu Xue
    • , Alex G. Hamilton
    •  & Michael J. Mitchell
  • Perspective
    | Open Access

    The development of human cellular models of aging that surpass the limitations of animal models of aging is urgent. Here, the authors explore the opportunities and limitations of cellular reprogramming to create reliable aging in vitro models and their potential for the discovery of anti-aging compounds.

    • Patricia R. Pitrez
    • , Luis M. Monteiro
    •  & Lino Ferreira
  • Article
    | Open Access

    The soil microbiome communicates with plant roots using a chemical language. Here, using p-coumaroyl-homoserine lactone as the synthetic communication signal, the authors demonstrate programmable microbe-to-plant communication from the sender in the soil bacteria to a receiver in the plant.

    • Alice Boo
    • , Tyler Toth
    •  & Christopher A. Voigt
  • Article
    | Open Access

    Manual processes to produce ocular prostheses are time-consuming and yield varying quality. Here, authors present an automatic digital end-to-end process for custom ocular prostheses. It creates shape and appearance from image data of an OCT device and produces them using a full-colour 3D printer.

    • Johann Reinhard
    • , Philipp Urban
    •  & Mandeep S. Sagoo
  • Article
    | Open Access

    Conventional blue denim dyeing has both environmental and health-related consequences. Here, Bidart et al. use enzyme engineering to develop a viable method for the bulk production of indican and demonstrate dying processes which could significantly reduce the negative consequences of this billion-dollar industry.

    • Gonzalo Nahuel Bidart
    • , David Teze
    •  & Ditte Hededam Welner
  • Article
    | Open Access

    Branched ionizable lipids have aroused great interest for mRNA delivery. Here, the authors devise an in situ construction method for combinatorial synthesis of degradable branched ionizable lipids and summarize key design criteria to enable potent delivery of mRNA therapeutics and gene editors.

    • Xuexiang Han
    • , Junchao Xu
    •  & Michael J. Mitchell
  • Article
    | Open Access

    The delivery of CRISPR RNPs has potential advantages over other genome editing approaches, including reduced off-target editing and reduced immunogenicity. Here the authors report self-deliverable Cas9 RNPs capable of robustly editing cultured cells in vitro and the mouse brain upon direct injections.

    • Kai Chen
    • , Elizabeth C. Stahl
    •  & Jennifer A. Doudna
  • Article
    | Open Access

    A key aim in the development of diagnostic assays is improving diagnostic speed while maintaining sensitivity. Here the authors report an approach for the rapid and accurate analysis of lateral flow tests, which integrates time-series deep learning and AI verification, achieving a diagnostic time of 1-2 minutes.

    • Seungmin Lee 
    • , Jeong Soo Park
    •  & Jeong Hoon Lee