Biotechnology articles within Nature Communications

RNA provides a unique readout of a cell’s identity, physiologic status, and phenotype. Here the authors deliver an RNA sensing system that can use the information contained within cellular RNA to selectively control the activity of genetic programs.

‘Manufacturing CAR-T cells is a streamlined and highly regulated procedure involving T-cell-expansion and activation on a standardised platform. Here, the authors show that a personalized approach, taking the phenotypic attributes of individual patients’ T cells into account, leads to more efficient CAR-T cell manufacturing and better CAR-T cell functionality.

Sensing small biomolecules in biofluids using host-guest chemosensors remains challenging, in part due to the impact of interfering components. Here, the authors develop a dual-macrocyclic rotaxane for tryptophan detection which can function in biofluids such as human serum and urine.

Spatial transcriptomics relies on RNA quality, which is variable and dependent on sample handling, storage, and/or intrinsic factors. Here, authors present a genome-wide spatial gene expression profiling method called RNA Rescue Spatial Transcriptomics (RRST), designed for the analysis of moderate to low quality fresh frozen tissue samples and demonstrate its robustness on 7 different tissue types.

Injectable biomimetic hydrogels hold significant promise for tissue engineering applications. Here, the authors present a hybrid myoglobin:peptide hydrogel to overcome a critical oxygen shortage following neural stem cell transplantation, thus increasing cell survival and integration.

Antigen display on outer membrane vesicles (OMVs) can be difficult to control and highly variable. Here, the authors describe a universal approach called AvidVax for linking biotinylated antigens to the exterior of OMVs and enabling rapid vaccine assembly.

Brassinolide (BL) is one of the most active compounds among phytohormone brassinosteroids (BRs) and can be used for plant growth and development regulation. Here, the authors report the construction of an artificial pathway in baker’s yeast for scalable production of 24-epi-ergosterol, a precursor for BL semi-synthesis.

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.

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.

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.

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.

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.

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.

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.

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.

Modification of RNA with N6-methyladenosine can regulate RNA metabolism. Here they developed scm⁶A-seq to profile the methylome and transcriptome in single cells, and reveal the functions of m⁶A modification during oocyte maturation and early embryo development.

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.

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.

Prime editing represents a great advance to the genome editing field but is currently limited by the editing efficiency. Here the authors look to improve the efficiency by recruiting target proteins and show that the transcription factor P65 could enhance the desired editing outcomes at different gene loci.

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.

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.

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.

Genomes usually contain multiple chromosomes. The paper reports on GALA, a computational framework for chromosome-based sequencing data separation and gap-free de novo assembly. It allows integration of different sources of data.

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.

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.

Here the authors generate an RNA-based platform to neutralize the major epigenetic player DNMT1. Using this targeted approach, aberrant DNA methylation in cancer can be corrected.

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.

The covid pandemic has highlighted the need for rapid antibody development. Here, authors develop an approach called SLISY, which uses NGS with phage display to simultaneously assess millions of clones to rapidly isolate specific antibodies against SARS-CoV-2 and its evolving variants.

Methods to predict genome-wide off-target activities of prime editors (PEs) are currently lacking. Here the authors report a cell-based assay, TAgmentation of Prime Editor sequencing (TAPE-seq), that provides genome-wide off-target candidates for PEs.

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.

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.

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.

Imaging non-repetitive loci in living cells remains challenging. Here, the authors engineered an inducible system whereby biomolecular assemblies can be guided to specific genomic loci by a nuclease-defective Cas9, allowing the simultaneous imaging and manipulation of the loci.

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.

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.

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.

Many viral diagnostic approaches require nucleic acid extraction and amplification prior to detection. Here, the authors develop a method based on type III CRISPR systems which allows sequence specific capture, concentration, and detection of viral RNA directly from patient samples.

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.

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.

PRPF31-RP is a blinding disease, caused by insufficient levels of a pre-mRNA splicing factor. Here, the authors show that CRISPR-Cas9 editing of the Prpf31 gene in mice leads to retinal degeneration similar to human patients, and, in the same model, demonstrate benefits from PRPF31 gene therapy.

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.

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.

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.

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.

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.

Current mesenchymal stem cell (MSC) transplantation practices are limited by the loss or reduced performance of MSCs. Here the authors develop a bead-jet printer for intraoperative formulation and printing of MSCs-laden Matrigel beads to improve skeletal muscle and hair follicle regeneration.

The probiotic Lactococcus lactis has been used for the delivery of therapeutic molecules. Here the authors engineer Lactococcus lactis to express a fusion protein of Flt3L and OX40 ligand, eliciting anti-tumor immune response in preclinical cancer models.

Retrotransposons are mobile genetic elements normally repressed by DNA methylation in differentiated cells. Here, the authors show that DNA hypomethylation in mouse induced pluripotent stem cells allows retrotransposons to jump, but this can be blocked with a reverse transcriptase inhibitor.

Fast screening of enzymes is key for directed evolution of industrial biocatalysts. Here, the authors report a simple, high-throughput, and low-equipment-dependent growth selection system for engineering three enzymes for synthesis of chiral amines.