Reviews & Analysis

A mini-colon device mimics colorectal tumors and their interactions with neighboring healthy tissue, stromal cells and immune cells.

We developed click editors, comprising HUH endonucleases, DNA-dependent DNA polymerases and CRISPR–Cas9 nickases, which together enable programmable precision genome engineering from simple DNA templates.

Improving the precision of gene correction through RNA base editing typically involves a trade-off with efficiency. We find using G•U wobble base pairs is a universally applicable strategy to improve editing precision and efficiency, and is effective in a mouse model of Rett syndrome in vivo.

Research on enzymatic RNA synthesis has long been eclipsed by work on DNA—but a new method provides a leap forward for RNA.

A therapeutic strategy harnesses evolutionary dynamics to overcome tumor resistance to targeted therapies.

Lab-grown ‘mini-colons’ enable the simulation of colorectal tumor dynamics and the high-resolution study of interactions with cells from the tumor’s native microenvironment. These next-generation organoids offer a wealth of new experimental opportunities, propelling the frontiers of cancer modeling in multiple directions.

We use a CRISPR screening platform based on adeno-associated virus and the Sleeping Beauty transposon (AAV-SB-CRISPR) to perform in vivo CRISPR screens in primary natural killer (NK) cells across four different tumor models, and identify calcium homeostasis modulator family member 2 (CALHM2) as an NK cellular checkpoint protein.

We developed SynTracker, a tool to track conspecific microbial strains using genome synteny. SynTracker is sensitive to genomic structural variation but not to single-nucleotide polymorphisms (SNPs). Combining SynTracker with methods for tracking strains using SNP profiles, we were able to detect species evolving by accumulating predominantly SNPs or predominantly structural variants.

By integrating confocal illumination along a moving axis with scanning light-field microscopy, confocal scanning light-field microscopy captures images with high spatiotemporal resolution and optical sectioning simultaneously, with low phototoxicity. This compact technique enabled us to investigate a wide variety of rapid subcellular 3D dynamics in vivo with high fidelity over extended periods.

To advance the toolset for controlling plant gene expression, we developed a CRISPR interference-based platform for the construction of synthetic Boolean logic gates that is functional in multiple plant species. These genetic circuits are programmable and reversible in nature, which will enable spatiotemporal control of plant responses to dynamic cues.

Two CRISPR tools for combinatorial genetic perturbations reveal gene regulatory networks.

A differentiation protocol to produce off-the-shelf natural killer T cells may enable clinical application.

The replicational age of single cells provides a temporal reference for tracking cell fate transition trajectories. The computational framework EpiTrace measures cell age using single-cell ATAC-seq data, specifically by considering chromatin accessibility at clock-like genomic loci, enabling the reconstruction of the history of developmental and pathological processes.

A strategy for creating drugs that can be quickly neutralized is demonstrated for anticoagulants.

A set of 20 computational metrics was evaluated to determine whether they could predict the functionality of synthetic enzyme sequences produced by generative protein models, resulting in the development of a computational filter, COMPSS, that increased experimental success rates by 50–150%, tested in over 500 natural and AI-generated enzymes.

Borderlands Science is a casual mini-game released within a mass-market video game that crowdsources the alignment of one million RNA sequences from the human microbiome. In 3 years, 4 million participants generated over 135 million puzzle solutions that were used to build a reference alignment and improve microbial phylogeny.

Using synthetic biology, we engineered a cellulose-producing bacterium that can produce eumelanin and respond to light, so that it is possible to grow a microbial leather material that is colored black or contains projected black patterns.

Cells interact with their local environment to enact global tissue function. By harnessing gene–gene covariation in cellular neighborhoods from spatial transcriptomics data, the covariance environment (COVET) niche representation and the environmental variational inference (ENVI) data integration method model phenotype–microenvironment interplay and reconstruct the spatial context of dissociated single-cell RNA sequencing datasets.

An engineered retrotransposon achieves targeted gene transfer into the human genome.

The underrepresentation of functional glial cells is a major challenge in brain organoid models. We developed an astroglia-enriched cortical organoid model that allows efficient generation of functional astrocytes and enables the formation of astroglial morphological subclasses with layer-specific gene expression profiles upon transplantation into the mouse brain.