Biotechnology

  • Article
    | Open Access

    Properties of cytidine and adenosine deaminases lead to off-target effects for cytosine base editors (CBEs) and adenine base editors (ABEs). Here the authors report that 25 TadA orthologs could be engineered to generate functional ABEs, CBEs or ACBEs via single/double mutations with minimised off-targets.

    • Shuqian Zhang
    • , Bo Yuan
    •  & Tian-Lin Cheng
  • Article
    | Open Access

    Hypercompact CRISPR-Cas12f systems have been engineered to generate miniABEs but these have limitations. Here the authors generate Cas12f-derived miniCBEs and develop miniABEs with improved editing and targeting scopes; they use these to correct pathogenic mutations in cell lines and introduce mutations in vivo.

    • Shuqian Zhang
    • , Liting Song
    •  & Tian-Lin Cheng
  • Article
    | Open Access

    Single-cell genomics has expanded to measure diverse molecular modalities within the same cell. Here the authors provide a computational framework called scTriangulate to integrate cluster annotations from diverse independent sources, algorithms, and modalities to define statistically stable populations.

    • Guangyuan Li
    • , Baobao Song
    •  & Nathan Salomonis
  • Article
    | Open Access

    Natural adhesives have received a lot of attention recently. Here, the authors develop a natural biological adhesive from snail mucus that can adhere to wet tissue and be used to accelerate healing of skin wounds.

    • Tuo Deng
    • , Dongxiu Gao
    •  & Mingyi Wu
  • Article
    | Open Access

    Differential sensing aims to mimic senses such as taste and smell through the use of synthetic receptors. Here, the authors show that arrays of de novo designed peptide assemblies can be used as sensor components to distinguish various analytes and complex mixtures.

    • William M. Dawson
    • , Kathryn L. Shelley
    •  & Derek N. Woolfson
  • Article
    | Open Access

    Hybrid nucleic acid origami has potential for biomedical delivery of mRNA and fabrication of artificial ribozymes. Here, the authors use chemical footprinting and cryo-electron microscopy to reveal insights into nucleic acid origami used to fold messenger and ribosomal RNA into 3D polyhedral structures.

    • Molly F. Parsons
    • , Matthew F. Allan
    •  & Mark Bathe
  • Article
    | Open Access

    Cryosurgery can represent a therapeutic option for breast cancer treatment. Here the authors report a strategy combining cryosurgery with cold-responsive nanoparticles loaded with the chemotherapeutic drug irinotecan and PD-L1-targeting siRNA, inducing anti-tumor immune responses in preclinical breast cancer models.

    • Wenquan Ou
    • , Samantha Stewart
    •  & Xiaoming He
  • Article
    | Open Access

    CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. Here the authors use transgenic lines with germline-specific regulatory elements to express Cas9 and achieve up to 94% inheritance bias, closing the gap between A. aegyptidrives and the highly efficient drives observed in Anopheles species.

    • Michelle A. E. Anderson
    • , Estela Gonzalez
    •  & Luke Alphey
  • Article
    | Open Access

    Gadolinium-neutron capture therapy (Gd-NCT) in glioblastoma shows promise but is limited by toxicity and short-half life in the brain. Here, the authors present a magnetised stem cell-nanoparticle system to facilitate brain penetrance of Gd-NCT and demonstrate its utility in an orthotopic rat glioblastoma model.

    • Yen-Ho Lai
    • , Chia-Yu Su
    •  & San-Yuan Chen
  • Article
    | Open Access

    Gene delivery to fibroblasts for liver fibrosis treatment remains challenging. Here the authors develop a combinatorial library of ligand-tethered lipidoids via a modular synthetic method and adopt a 2-round screening strategy to identify lipidoids for potent and selective gene delivery to fibroblasts.

    • Xuexiang Han
    • , Ningqiang Gong
    •  & Michael J. Mitchell
  • Article
    | Open Access

    Alveolar macrophages represent a cell type that is physiologic to the lung immune landscape, however, it is not known whether they play an active role to maintain the tumour immune microenvironment. Here authors show by single cell RNA sequencing and functional experiments, that intra-tumour alveolar macrophages are phenotypically and transcriptionally different from the healthy ones, and likely play an aetio-pathologic role in tumorigenesis.

    • Seiji Taniguchi
    • , Takahiro Matsui
    •  & Masaru Ishii
  • Review Article
    | Open Access

    CRISPR-Cas tools have shown exceptional promise in genome engineering over the past decade. Here the authors review the development of CRISPR-Cas9/Cas12/Cas13 nucleases, DNA base editors, prime editors, and RNA base editors, as well as their editing precision, off-target effects, and clinical considerations.

    • Jianli Tao
    • , Daniel E. Bauer
    •  & Roberto Chiarle
  • Article
    | Open Access

    Volumetric additive manufacturing of protein scaffolds has a wide range of possible biomedical applications. Here the authors report on the bioprinting of unmodified silk sericin and silk fibroin inks with shape-memory and tuneable mechanical properties and demonstrate the potential of the inks in different applications.

    • Maobin Xie
    • , Liming Lian
    •  & Yu Shrike Zhang
  • Article
    | Open Access

    Here, Liao and colleagues apply adenine base editor ABE8e and its PAM-less variant ABE8e-SpRY to β-thalassemia patient hematopoietic stem cells in the form of ribonucleoprotein complexes, resulting in efficient long-term editing and β-thalassemia alleviation.

    • Jiaoyang Liao
    • , Shuanghong Chen
    •  & Yuxuan Wu
  • Article
    | Open Access

    Bioengineering live tissues has remained challenging due to limited nutrient exchange in the growing tissues. Here, the authors have developed micro-perfused 2-photon printing of 3D microfluidics, to engineer large-scale, viable and functional neural and hepatic 3D tissues.

    • Sergei Grebenyuk
    • , Abdel Rahman Abdel Fattah
    •  & Adrian Ranga
  • Article
    | Open Access

    Aromatic amino acids in proteins support ligand binding and protein stability. To parse the physiocochemical roles of aromatic interactions, here Galles, Infield and co-authors identify pyrrolysine-based aminoacyl-tRNA synthetases that enable the encoding of fluorinated phenylalanine amino acids.

    • Grace D. Galles
    • , Daniel T. Infield
    •  & Christopher A. Ahern
  • Article
    | Open Access

    Previously, a proof-of-concept for low frequency synthetic apomixis was established in a laboratory strain of rice by combining MiMe mutations with the egg cell expression of the embryogenic trigger - BBM1. Here, the authors achieve clonal seed formation in hybrid rice with almost full penetrance and higher fertility.

    • Aurore Vernet
    • , Donaldo Meynard
    •  & Emmanuel Guiderdoni
  • Article
    | Open Access

    Islet transplantation for type 1 diabetes management is hindered by the life-long need for immunosuppressive medications. Here, the authors report an islet encapsulation device with local anti-rejection drug release that achieves long-term diabetes reversal in male rats and reduces drug-related toxicity.

    • Jesus Paez-Mayorga
    • , Jocelyn Nikita Campa-Carranza
    •  & Alessandro Grattoni
  • Article
    | Open Access

    The interplay between histone modifications and DNA methylation plays a crucial role in establishing and maintaining the epigenomic landscape. Here, the authors develop a nanopore sequencing based method for mapping histone modifications and DNA methylation from native, long, single DNA molecules.

    • Xue Yue
    • , Zhiyuan Xie
    •  & Yimeng Yin
  • Article
    | Open Access

    Longitudinal proteomics holds great promise for biomarker discovery, but the data interpretation has remained a challenge. Here, the authors evaluate several tools to detect longitudinal differential expression in proteomics data and introduce RolDE, a robust reproducibility optimization approach.

    • Tommi Välikangas
    • , Tomi Suomi
    •  & Laura L. Elo
  • Article
    | Open Access

    Undesired chromosomal translocations, vector integrations, and large deletions remain a problem for therapeutic gene editing in vivo. Here, the authors compare the CRISPR-Cas9TX variant with CRISPR-Cas9 and show elimination of chromosomal translocations and reduction of AVV integration when targeting Vegfa for the treatment of age-related macular degeneration in a mouse model.

    • Jianhang Yin
    • , Kailun Fang
    •  & Jiazhi Hu
  • Article
    | Open Access

    Neoadjuvant chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer, however, response can be limited by development of toxicities. Here, the authors conducted metabolomics on patients with locally advanced rectal cancer enrolled in a phase III clinical study and identify serum metabolites associated with treatment response.

    • Hongmiao Wang
    • , Huixun Jia
    •  & Zheng-Jiang Zhu
  • Article
    | Open Access

    Programmable, RNA-guided nucleases are diverse enzymes that have been repurposed for biotechnological applications. Here, the authors mine an extensive genome-resolved metagenomics database and identified uncharacterized families of RNA-guided, compact nucleases.

    • Daniela S. Aliaga Goltsman
    • , Lisa M. Alexander
    •  & Christopher T. Brown
  • Article
    | Open Access

    The biosynthetic pathway of type II ganoderic acids (GAs) in Ganoderma lucidum, a traditional medicinal mushroom, is unknown. Here, the authors assemble the genome of type II GAs accumulating accession, identify CYPs involving in type II GAs biosynthesis, and achieve their production in engineered baker’s yeast.

    • Wei Yuan
    • , Chenjian Jiang
    •  & Han Xiao
  • Article
    | Open Access

    Nacre structure is used as inspiration in the design of impact resistant materials yet natural nacre is overcome by high impact speed attacks from predators. Here, the authors perform a range of testing and demonstrate superior energy dissipation of nacre-like structures at low impact velocities which is lost at higher impact velocities.

    • Xiao Zhang
    • , Kaijin Wu
    •  & Linghui He
  • Article
    | Open Access

    Comprehensive annotating of cell types in spatially resolved transcriptomics to understand biological processes at the single cell level remains challenging. Here the authors introduce Spatial-ID, a supervision-based cell typing method, that combines the existing knowledge of reference single-cell RNA-seq data and the spatial information of spatially resolved transcriptomics data.

    • Rongbo Shen
    • , Lin Liu
    •  & Jianhua Yao
  • Article
    | Open Access

    The development of broad-spectrum antivirals is an important part of pandemic preparedness and response. Here the authors present ALICE, synthetic biology designer immune-like cells that act as a sense-and-destroy antiviral system can detect viruses from seven different genera, mimicking the human innate immune system.

    • Yidan Wang
    • , Ying Xu
    •  & Haifeng Ye
  • Article
    | Open Access

    Despite the importance of DNA methylation, accessible and high-throughput methods to profile methylation at the single-cell level are lacking. Here, the authors present sciMETv2, a high-throughput workflow that provides high-quality single-cell methylomes in a robust and simple workflow.

    • Ruth V. Nichols
    • , Brendan L. O’Connell
    •  & Andrew C. Adey
  • Article
    | Open Access

    Off-target binding hinders the development of therapeutic antibodies and reproducibility in basic research settings. Here the authors develop a method to quantify and reduce the polyreactivity of antibody fragments based on protein sequence alone.

    • Edward P. Harvey
    • , Jung-Eun Shin
    •  & Andrew C. Kruse
  • Article
    | Open Access

    Retrosynthetic pathway design using promiscuous enzymes can provide a solution to the biosynthetic production of natural products. Here, the authors design a pathway for the production of cis-α-irone with a promiscuous methyltransferase using structure-guided enzyme engineering strategies.

    • Xixian Chen
    • , Rehka T
    •  & Isabelle André
  • Article
    | Open Access

    Multiple sclerosis is a debilitating autoimmune disease, for which therapy is not curative, only slowing down progression at the expense of general immune suppression. Here authors show that in a mouse model of multiple sclerosis, disease progression could be halted or even reversed by a nanovaccine, composed of reactive oxygen species scavenging cerium oxide nanoparticles, which establishes immune tolerance against the relevant autoantigen.

    • Thanh Loc Nguyen
    • , Youngjin Choi
    •  & Jaeyun Kim
  • Article
    | Open Access

    Heparin is a family of complex carbohydrates binding to proteins to modulate cell activities. Here the authors report the synthesis, and conformations simulations of S-linked hemi-A heparosan [GlcA-S-GlcNAc]n, a thio-glycosidic uncleavable polysaccharide, and test it as human heparanase inhibitor.

    • Peng He
    • , Xing Zhang
    •  & Paul L. DeAngelis
  • Article
    | Open Access

    In situ generated lesion of red blood cells decreases the quality of stored blood and limits its shelf-life. Here, the authors demonstrate that intermittent scavenging of storage lesions using electrostatic interactions by nanofibrous sheets could enhance the quality and shelf-life of stored blood.

    • Subhashini Pandey
    • , Manohar Mahato
    •  & Praveen Kumar Vemula
  • Article
    | Open Access

    Here, authors show that precise integration of an rAAV vector into a chromosomal target locus results in expression of a self-cleaving guide RNA. This recombination event creates genetic resistance to a hepatotoxic compound and enables in vivo expansion of gene-edited hepatocytes using a selection drug.

    • Amita Tiyaboonchai
    • , Anne Vonada
    •  & Markus Grompe
  • Article
    | Open Access

    Chemical injuries to the eye are medical emergencies with limited acute treatment options and can cause permanent vision loss. Here, the authors show that perfluorodecalin-based supersaturated oxygen emulsion is a safe and effective topical therapeutic in treating acute ocular chemical burn by reducing tissue hypoxia and inflammation.

    • Sanming Li
    • , Kunpeng Pang
    •  & Jia Yin