RNA–protein interaction networks govern many biological processes but are difficult to examine comprehensively. We devised ribonucleoprotein networks analyzed by mutational profiling (RNP-MaP), a live-cell chemical probing strategy that maps cooperative interactions among multiple proteins bound to single RNA molecules at nucleotide resolution. RNP-MaP uses a hetero-bifunctional crosslinker to freeze

Correct reconstruction of macromolecular structure by cryo-electron microscopy (cryo-EM) relies on accurate determination of the orientation of single-particle images. For small (<100 kDa) DNA-binding proteins, obtaining particle images with sufficiently asymmetric features to correctly guide alignment is challenging. We apply DNA origami to construct molecular goniometers—instruments that precisely

Depletion of mitochondrial copper, which shifts metabolism from respiration to glycolysis and reduces energy production, is known to be effective against cancer types that depend on oxidative phosphorylation. However, existing copper chelators are too toxic or ineffective for cancer treatment. Here we develop a safe, mitochondria-targeted, copper-depleting nanoparticle (CDN) and test it against triple-negative

Current approaches to single-cell RNA sequencing (RNA-seq) provide only limited information about the dynamics of gene expression. Here we present RNA timestamps, a method for inferring the age of individual RNAs in RNA-seq data by exploiting RNA editing. To introduce timestamps, we tag RNA with a reporter motif consisting of multiple MS2 binding sites that recruit the adenosine deaminase ADAR2 fused

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The potential of genome editing to improve the agronomic performance of crops is often limited by low plant regeneration efficiencies and few transformable genotypes. Here, we show that expression of a fusion protein combining wheat GROWTH-REGULATING FACTOR 4 (GRF4) and its cofactor GRF-INTERACTING FACTOR 1 (GIF1) substantially increases the efficiency and speed of regeneration in wheat, triticale

Recent patents related to methods for the mass production of exosomes and engineering of exosomes for therapeutic use.

Inhaled RNA is coming soon for countermeasures against respiratory pathogens, including COVID-19.

A national network of medical technology incubators provides experiential training for the next generation of medical entrepreneurs and enables creation of innovative technologies for pressing clinical needs.

The agency’s ‘no-go’ for BioMarin’s hemophilia A gene therapy came as a surprise, but reflects outstanding questions as to the durability of the treatment.

Voluntary pledges to make intellectual property broadly available to address urgent public health crises can overcome administrative and legal hurdles faced by more elaborate legal arrangements such as patent pools and achieve greater acceptance than governmental compulsory licensing.

Several startups are now pursuing the potential of enzymatic synthesis as a faster and more efficient route for synthesizing longer DNA sequences than is possible with traditional chemical means.

Recent moves of note in and around the biotech and pharma industries.

Wild and weedy relatives of domesticated crops harbor genetic variants that can advance agricultural biotechnology. Here we provide a genome resource for the wild plant green millet (Setaria viridis), a model species for studies of C4 grasses, and use the resource to probe domestication genes in the close crop relative foxtail millet (Setaria italica). We produced a platinum-quality genome assembly

Achieving temporally precise, noninvasive control over specific neural cell types in the deep brain would advance the study of nervous system function. Here we use the potent channelrhodopsin ChRmine to achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at unprecedented depths of up to 7 mm with millisecond precision. Using systemic viral delivery

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nature Biotechnology convenes a group of experts to provide their insights into SARS-CoV-2 vaccines in development.

Plasma from individuals who have recovered from COVID-19 could benefit sick patients, but definitive evidence for or against convalescent plasma is still lacking. A consensus about how it should be deployed is beginning to emerge—and tools and insights to guide its use are becoming available.

The scientific integrity of US government agencies is under attack from the Trump administration. Agency senior executives and industry leaders need to continue pushing back.

Wastewater testing captures the rise and fall of novel coronavirus cases in a mid-sized metropolitan region.

Prime editing enables the introduction of virtually any small-sized genetic change without requiring donor DNA or double-strand breaks. However, evaluation of prime editing efficiency requires time-consuming experiments, and the factors that affect efficiency have not been extensively investigated. In this study, we performed high-throughput evaluation of prime editor 2 (PE2) activities in human cells

Activation of nociceptor sensory neurons by noxious stimuli both triggers pain and increases capillary permeability and blood flow to produce neurogenic inflammation1,2, but whether nociceptors also interact with the immune system remains poorly understood. Here we report a neurotechnology for selective epineural optogenetic neuromodulation of nociceptors and demonstrate that nociceptor activation

We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentrations in primary sewage sludge in the New Haven, Connecticut, USA, metropolitan area during the Coronavirus Disease 2019 (COVID-19) outbreak in Spring 2020. SARS-CoV-2 RNA was detected throughout the more than 10-week study and, when adjusted for time lags, tracked the rise and fall of cases seen in SARS-CoV-2 clinical

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Can traditional computational analysis and machine learning help compensate for inadequate peer review of drug-repurposing papers in the context of an infodemic?

Tumor-specific elucidation of physical and functional oncoprotein interactions could improve tumorigenic mechanism characterization and therapeutic response prediction. Current interaction models and pathways, however, lack context specificity and are not oncoprotein specific. We introduce SigMaps as context-specific networks, comprising modulators, effectors and cognate binding-partners of a specific

The Chan Zuckerberg Biohub is both an institute and an academic network devoted to accelerating research via cutting edge technologies and open science. Its focus on single-cell analysis and infectious disease has placed it front and center in the pandemic.

Brain–computer interfaces (BCIs) enable control of assistive devices in individuals with severe motor impairments. A limitation of BCIs that has hindered real-world adoption is poor long-term reliability and lengthy daily recalibration times. To develop methods that allow stable performance without recalibration, we used a 128-channel chronic electrocorticography (ECoG) implant in a paralyzed individual

Engineered SpCas9s and AsCas12a cleave fewer off-target genomic sites than wild-type (wt) Cas9. However, understanding their fidelity, mechanisms and cleavage outcomes requires systematic profiling across mispaired target DNAs. Here we describe NucleaSeq—nuclease digestion and deep sequencing—a massively parallel platform that measures the cleavage kinetics and time-resolved cleavage products for over

Monitoring the T cell receptor (TCR) repertoire in health and disease can provide key insights into adaptive immune responses, but the accuracy of current TCR sequencing (TCRseq) methods is unclear. In this study, we systematically compared the results of nine commercial and academic TCRseq methods, including six rapid amplification of complementary DNA ends (RACE)-polymerase chain reaction (PCR) and

Recent patents related to new biomarkers and methods of transcriptomic data analysis and integration.

A deep brain stimulation device capable of fine-tuning output on the basis of patient neuronal activity has been approved for the first time for use in Parkinson’s and a range of other neurological disorders.

Initiatives to gather massive epidemiological datasets aim to cut through national COVID-19 stats in a bid to understand the new coronavirus and aid public health policymakers.

The interaction between patents and FDA’s De Novo and 510(k) regulatory pathways has the potential to threaten follow-on innovation for medical devices.

A new workshop brings together under-represented participants to gain experience working in diverse teams, identifying problems worth solving, and learning evidence-based entrepreneurship approaches.

Recent moves of note in and around the biotech and pharma industries.

Four antibodies are already in trials to test efficacy against the emerging checkpoint molecule TIGIT, but debate swirls around the importance of Fc binding for drug action.

Single-cell barcoding technologies enable genome sequencing of thousands of individual cells in parallel, but with extremely low sequencing coverage (<0.05×) per cell. While the total copy number of large multi-megabase segments can be derived from such data, important allele-specific mutations—such as copy-neutral loss of heterozygosity (LOH) in cancer—are missed. We introduce copy-number haplotype

The translational power of human microbiome studies is limited by high interindividual variation. We describe a dimensionality reduction tool, compositional tensor factorization (CTF), that incorporates information from the same host across multiple samples to reveal patterns driving differences in microbial composition across phenotypes. CTF identifies robust patterns in sparse compositional datasets

Cellular metabolism regulates immune cell activation, differentiation and effector functions, but current metabolic approaches lack single-cell resolution and simultaneous characterization of cellular phenotype. In this study, we developed an approach to characterize the metabolic regulome of single cells together with their phenotypic identity. The method, termed single-cell metabolic regulome profiling

The pandemic has highlighted long-standing, deep-rooted challenges to the sharing of biological samples. Greater attention is needed to mechanisms for incentivizing materials transfer.

Appropriate use and interpretation of serological tests for assessments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, infection and potential immunity require accurate data on assay performance. We conducted a head-to-head evaluation of ten point-of-care-style lateral flow assays (LFAs) and two laboratory-based enzyme-linked immunosorbent assays to detect anti-SARS-CoV-2

Determining the spatial organization of chromatin in cells mainly relies on crosslinking-based chromosome conformation capture techniques, but resolution and signal-to-noise ratio of these approaches is limited by interference from DNA-bound proteins. Here we introduce chemical-crosslinking assisted proximity capture (CAP-C), a method that uses multifunctional chemical crosslinkers with defined sizes

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Natural mitochondrial DNA (mtDNA) mutations enable the inference of clonal relationships among cells. mtDNA can be profiled along with measures of cell state, but has not yet been combined with the massively parallel approaches needed to tackle the complexity of human tissue. Here, we introduce a high-throughput, droplet-based mitochondrial single-cell assay for transposase-accessible chromatin with

Single-cell analysis sheds light on immune response to COVID-19 infection, enables the rapid discovery of antibody leads, and points to ways to get ahead of future pandemics.

A detailed understanding of the function of neural networks and how they are supported by a dynamic vascular system requires fast three-dimensional imaging in thick tissues. Here we present confocal light field microscopy, a method that enables fast volumetric imaging in the brain at depths of hundreds of micrometers. It uses a generalized confocal detection scheme that selectively collects fluorescent

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Recent patents related to systems and methods of imaging.

If the decision is allowed to stand, it will have major implications for pharmaceutical patents and biomedical innovation.