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This Review discusses strategies for the genetic engineering of adoptive T cell immunotherapies with a focus on approaches harnessing transgenic T cell receptors or chimeric antigen receptors to treat cancer. The authors also discuss the more complex levels of genetic regulation that will be needed to ensure both safety and efficacy.
Interactions between microorganisms and their hosts are highly context dependent and contribute to both normal tissue function and infectious disease pathology. In this Review, Westermann and Vogel describe how advances in RNA sequencing techniques are providing molecular insights into host–microbe interactions, including advances in cross-species and single-cell transcriptomics.
There is a rapidly growing appreciation of the complexities of 3D genome organization, as well as associations with gene expression and wider cellular and organismal phenotypes, including diseases. In this Review, the authors describe diverse experimental methods for manipulating 3D genome organization — from fine-scale control of DNA contacts to large-scale nuclear repositioning — which are facilitating detailed testing of the biological functions of 3D genome organization.
Maintenance of cell-type identity requires the faithful inheritance of chromatin states through cell division, despite the challenges posed by the disruptive passage of the DNA replication fork and the dilution of nucleosome components in complex with the daughter DNA strands. In this Review, Escobar, Loyola and Reinberg discuss how methodological advances are providing unprecedented mechanistic insights into the segregation of parental nucleosomes, how these mechanisms maintain gene expression programmes and how non-faithful nucleosome segregation is linked to differentiation and disease.
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.
