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The application of CRISPR–Cas13 for targeted RNA degradation is hindered by the existence of collateral effects induced by Cas13. We screened hundreds of engineered Cas13 variants using a convenient and sensitive reporter system and obtained several variants with markedly reduced collateral activity and efficient on-target activity, suitable for in vivo applications.
Porcine dermal collagen was chemically and photochemically bioengineered into an implantable tissue mimicking the human corneal extracellular matrix. The implant presents a simpler and safer method than donor cornea transplantation while delivering equivalent outcomes, and has restored vision to people with advanced keratoconus in resource-limited regions, where the burden of blindness is highest.
This study reveals a high level of behavioral heterogeneity in engineered T cells that target tumor organoids. Behavior-guided transcriptomics identified the gene signatures of T cells with highly potent serial cytotoxicity. Integration of the organoid and T cell transcriptomic data enabled the design of patient-specific combinatorial treatment to achieve an optimized response to cancer immunotherapies.
Genomic surveillance is important for pandemic preparedness. By deep sequencing of wastewater samples, we monitored the genetic dynamics of circulating SARS-CoV-2 virus variants in Austria from December 2020 to February 2022. We show how wastewater-based epidemiology enables robust quantification of viral spatiotemporal dynamics as well as the detection of emergent new variants.
Many biomedical questions demand scalable, deep, and accurate proteome analysis of small samples, including single cells. A scalable framework of multiplexed data-independent acquisition for mass spectrometry enables time saving by parallel analysis of both peptide ions and protein samples, thereby realizing multiplicative gains in throughput.
Drug combinations predicted to increase tumor cell death directly and by creating strong antitumor tumor microenvironments were identified by computational analysis of local responses to combinations of anticancer drugs delivered inside a tumor. Such predicted drug combinations were highly effective when administered systemically in mouse models of breast cancer.
Current high-throughput single-cell methods detect only a small part of the transcriptome. The workflow presented here integrates molecular analysis and droplet microfluidics to derive total transcriptomic atlases that encompass alternative splicing and non-coding transcripts in large numbers of single cells. The utility of this method is demonstrated by analysis of mouse gastrulation and early organogenesis.
The Tibetan glacier genome and gene catalog includes 3,241 metagenome-assembled or cultured genomes spanning 30 phyla and over 25 million genes encoding non-redundant proteins. This catalog provides a wealth of resources for archiving glacier microbial diversity and bioprospecting for bioactive compounds, as well as a platform for global comparison of glacier microbiomes.
Most plant hormone sensors, including the abscisic acid receptor PYR1, function through chemically induced dimerization. Using computationally designed libraries of PYR1, we created high-affinity receptors for 21 structurally diverse ligands, setting the stage for large-scale small-molecule biosensor development
We developed two quantitative PCR-based assays to detect SARS-CoV-2-specific T cell immunity: qTACT and dqTACT. The assays quantify CXCL10 mRNA, after incubation of whole blood with viral peptides, as a proxy of an antigen-specific T cell response, and will allow population-level monitoring of cellular immunity to SARS-CoV-2.
A new study describes a microscope combining three-photon excitation and adaptive optics capable of high-resolution in vivo imaging of fine neuronal structures in the mouse cortex through the intact skull. The authors demonstrate the use of this platform to guide precise laser-mediated microsurgery and for accurate and sensitive functional calcium imaging.
Reprogramming of antibody responses in mice is achieved via adeno-associated virus delivery of SaCas9, single guide RNA (sgRNA) and a repair template targeting immunoglobulin genes.
RNA interference (RNAi) therapeutics can silence disease-causing gene transcripts, but extrahepatic delivery has been challenging. Conjugating short interfering RNAs (siRNAs) to a lipophilic alkyl chain enabled safe delivery and long-term mRNA silencing in the brain, eye and lung in animal models, thereby opening new applications for RNAi therapeutics.
Existing technologies can map the intricate spatial distribution of biomolecules and cell types within tissues, but not in specimens that remain alive and intact. This study introduces scission-accelerated fluorophore exchange (SAFE) bioorthogonal imaging tools that enable living cells and tissues to be deeply and serially profiled, revealing their biological dynamics across both space and time.
Our multidisciplinary team used novel perfusion technology to successfully keep an injured liver graft discarded by all other centers alive for several days, allowing proper graft evaluation and repair. The graft was successfully transplanted into a sick patient, who recovered quickly and enjoyed a normal life at one-year follow up.
Are major decisions in the cell made through pairs of interacting loci (enhancers and promoters) or larger teams of cooperating regulatory elements? A new genome-wide assay and algorithm answers this question and provides a scalable technology to link new dimensions of genome structure with cellular function.
By quantifying thousands of proteins in tumor cells in an unbiased manner, Deep Visual Proteomics uncovers mechanisms that drive tumor evolution and reveals new therapeutic targets. The method incorporates advanced microscopy, artificial intelligence and ultra-high-sensitivity proteomics to characterize individual cell identities.
