MicroRNAs (miRNA) exert essential functions in mammalian development and physiology. The authors review recent insights from the phenotypic analysis of miRNA knockouts in mice that emphasize roles for these non-coding RNAs at different developmental stages and in adults, and illustrate the importance of functional miRNA targets, miRNA dosage, miRNA interactions and cellular context.

Shadow enhancers regulate a common target gene and drive expression patterns that overlap spatiotemporally. The authors review recent insights into the prevalence and role of shadow enhancers in metazoans, as well as their mechanisms of action to fine-tune gene expression. They also discuss the evolution of shadow enhancers and their implication in disease.

Africa is a continent with deep evolutionary history, which has implications for the genetic underpinnings of disease. In this Review, the authors discuss how genetic features of African populations provide both challenges and opportunities for understanding disease genetics in Africa. They describe how this genetic knowledge — combined with initiatives including capacity-building, data sharing and increased representation of African genomes in genetic variation databases — can be leveraged towards achieving precision medicine approaches in African healthcare.

Our evolutionary history has resulted in highly complex and sophisticated human physiology. Yet evolutionary footprints have also left us prone to diseases. In this Review, the authors discuss how events from the earliest history of life on Earth through to modern human evolution influence many disease traits and outcomes. They describe how an understanding and application of evolutionary frameworks can inform precision medicine initiatives.

The ability to reprogramme cellular translation and genomes to produce non-canonical biopolymers has wide-ranging applications, including in therapeutics, but has yet to be fully realized. In this Review, de la Torre and Chin discuss recent advances towards achieving this goal.

Haematopoietic stem and progenitor cell (HSPC) gene therapy using lentiviral or gammaretroviral vectors has now been approved for clinical use. In this Review, Ferrari, Thrasher and Aiuti discuss the history of HSPC gene therapy, the clinical promise of gene-editing HPSCs and the use of HSPC gene therapy to treat specific diseases.

A report in Science describes in situ genome sequencing (IGS), a method that enables genomes to be simultaneously sequenced and imaged in intact samples, including early mouse embryos. IGS will facilitate insight into the relationship between genome sequence and organization.

A study in Nature Genetics applies whole-genome sequencing to monozygotic twins, their parents, partners and offspring to identify and characterize early developmental mutations, as well as the fate of mutated cells.

A study in Nature reports that adenine base editors can correct the mutation that causes Hutchinson–Gilford progeria syndrome in a mouse model of this disease, extending lifespan.

Two new papers in Nature Biotechnology report methods for targeted sequencing of complex DNA samples, achieved in real time during nanopore sequencing runs.

An article in Cell describes a multi-omic analysis of health risks from spaceflights that implicates mitochondrial stress and dysregulation as key drivers.

A study in Genome Biology uses EpiGo-KRAB to analyse the roles of H3K9me3 in genome organization and transcriptional repression and reveals the two functions may be distinct.