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Authors show that base editing can convert sickle hemoglobin (HbS) to the rare but naturally occurring variant G-Makassar (HbG). Purified HbG appears normal, but in a mouse model, HbGS red cells sickle under hypoxia, highlighting the importance of assessing red cell quality when evaluating novel gene editing strategies for hematologic disorders.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

An endothelialized microfluidic system that recapitulates physiological properties of the microvasculature enables the real-time visualization of vascular-pathology features associated with sickle-cell disease and malaria, with high spatiotemporal resolution.

Using data from 142,238 Mass General Brigham Biobank participants, researchers explored population history and social and genetic risk factors for disease in Greater Boston. The study links genetics and context to guide equitable precision health.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

MultiSuSiE is an extension of the Sum of Single Effects fine-mapping model that allows causal effect sizes to vary across ancestries. Applying MultiSuSiE to quantitative traits in All of Us identifies fine-mapped variants not implicated by other methods.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Antibodies against Plasmodium falciparum glutamic-acid-rich protein (PfGARP), an antigen expressed on the surface of infected red blood cells, kill P. falciparum parasites by inducing programmed cell death and reduce the risk of severe malaria.

A large-scale mutagenesis screen identifies mutant phenotypes for over 11,000 protein-coding genes in bacteria that had previously not been assigned a specific function.

The linking of salicylaldehydes to a kinase binding scaffold resulted in the development of reversible, lysine-targeted covalent kinase inhibitors with enhanced residence time.

A systematic implementation of six efficiency optimizations for prime editing led to high levels of functional correction, in airway epithelial cells, of the predominant mutation that causes cystic fibrosis.

Despite large sequencing and data sharing efforts it often remains challenging to provide a genetic diagnosis for individuals with suspected Mendelian (single-gene) disorders. Here, the authors describe their experiences in identifying likely causal genetic variants in thousands of families and highlight the need to consider a wide range of challenges rather than a narrow focus on sequencing technologies.

The role of coagulation factor FXII in diabetic kidney disease (DKD) remains unknown. Here, the authors show that zymogen FXII induces kidney injury via receptor (uPAR)-mediated signaling by inducing oxidative DNA damage and senescence, identifying new potential therapeutic targets for DKD.

Changes in muscovite caused by environmental factors can be detected in nanoindentation data with a statistical physics model for plastic deformation. The model’s simplicity implies these findings may generalize to other layered materials.

Improved cytosine base editors are generated by phage-assisted evolution of a deoxyadenosine deaminase.

This Perspective proposes a new framework that integrates large-scale population data with clinical evidence to improve disease risk assessment of genetic variants, enhancing the accuracy and value of genetic information in precision medicine.

Methane production is traditionally not found in oxygenated soils, a paradigm incorporated in global greenhouse gas modelling efforts. Here the authors show geochemical and biological evidence of active methanogenesis in bulk-oxic wetland soils, attributing up to 80% of the total methane budget for the site.

A deep chemical proteomic investigation of diverse aminophilic electrophiles has identified ligandable lysines across a wide range of human proteins. The proteins cover different functional and structural classes, and the aminophilic electrophiles include compounds that disrupt protein–protein and protein–RNA interactions. This dataset provides a proteome-wide atlas of lysine-reactive chemistry.

This protocol describes prime editing (PE) and twinPE experiments as well as the design and optimization of pegRNAs. The authors provide guidelines for selecting the proper PE system for a given application and how to perform PE in mammalian cells.

The patentability of genes is a controversial issue. As a partial remedy, many countries have exemptions from patent liability for non-commercial research. However, these exemptions are themselves problematic. The authors examine solutions to the problem and advocate the abolition of gene patents.

Diversification of the antibody repertoire is well known to be driven by genetic recombination and mutation. However, it is becoming apparent that other processes can also diversify antibody specificities. Here, Dimitrov and colleagues discuss these unconventional strategies for antibody diversification and consider why these extra strategies have evolved.

The current ‘second space age’ has enabled multiple studies on the effects of spaceflight on human physiology and health, which are contributing to the development of measures that will be needed to maintain astronaut health in future space missions.

A comparison of the frequency of pathogenic mutations in 73 genes in the All of Us cohort highlights the differences in pathogenic variation attributed to ancestry.

Keri Monda, Kari North, Christopher Haiman and colleagues report a meta-analysis of GWAS for body mass index that is composed of 39,144 individuals of African ancestry, followed by further genotyping in 32,268 individuals of African ancestry. The study also includes analysis of publicly available data from the GIANT consortium of ~124,000 individuals of European ancestry. The paper reports evidence for two new loci near GALNT10 and MIR148A.