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Delivering functional proteins or protein complexes into cells continues to be a significant challenge. Here, the authors develop efficient systems by using engineered extracellular vesicles to deliver functional cargoes, including CRISPR/Cas9-ribonucleoproteins, both in vitro and in vivo.

Yi et al. report that EZH2 exerts a PRC2-independent function in nucleoli, where it bridges FBL and NOP56 to facilitate rRNA methylation and subsequent IRES-dependent translation.

A vaccine targeting stress proteins expressed by many cancers blocks a tumour escape mechanism, enabling protective immunity mediated by diverse T cell and NK cell populations.

Using different genetic mice models, Sung et al. show that VEGF-C/VEGFR3 signaling is required for sinusoidal vascular growth in the fetal liver and bone marrow. CDH5 (VE-cadherin) negatively regulates VEGF-C/VEGFR3 signaling and sinusoidal and lymphatic growth. Loss of CDH5 enables growth of sinusoidal and lymphatic vessels in the absence of VEGFR3 signaling through VEGF-C/VEGFR2 signaling.

Comprenhensive analysis of human antibody responses to SARS-CoV-2 variants and animal sarbecoviruses finds that Omicron escapes neutralization more readily than distantly related animal sarbecoviruses.

A depolymerization method is described that uses electrified spatiotemporal heating to selectively generate monomers from the commodity plastics polypropylene and poly(ethylene terephthalate), allowing control over the pyrolysis of plastic waste and reducing the formation of side products.

Vaccination and infection history determine the breadth of neutralizing antibody response to SARS-CoV-2 variants and other sarbecoviruses with breakthrough or natural infection combined with vaccination or booster vaccination with mRNA vaccine providing highest neutralization.

Osteogenesis imperfecta (OI) is genetically linked to autosomal dominant or autosomal recessive mutations. Here, Marini et al. describe two families with X-chromosome-linked OI with mutations in MBTPS2 that alter regulated intramembrane proteolysis and subsequent defects in collagen crosslinking and osteoblast function.

Vaccine efficiency is enhanced by mesoporous silica rods that spontaneously form a 3D microenvironment for immune cells.

The immunosuppressive tumour microenvironment impairs immunotherapy in poorly immunogenic cancer. Here, the authors load an alginate gel with GM-CSF, CpG oligonucleotides and doxorubicin-iRGD to promote immunogenic death of tumour cells and improve immunotherapy efficacy in triple negative breast cancer models.

Injectable biomaterial vaccines designed to magnetically capture pathogen-associated molecular patterns protect mice and pigs against septic shock from lethal bacterial infections.

An extensive global transcriptomics analysis of in vivo responses to 86 cytokines across more than 17 immune cell types reveals enormous complexity of cellular responses to cytokines, providing the basis of the Immune Dictionary and its companion software Immune Response Enrichment Analysis.

The instability of DNA nanostructures in physiological environments has hampered their use as therapeutics and diagnostic agents inin vivoapplications. Here, the authors show that coating DNA origami with oligolysine-PEG moieties improves their pharmacokinetic properties in mouse models.

Dendritic cells concentrated in vivo within a hydrogel have been metabolically tagged with azido groups to enable tracking as well as delivery of antigens, adjuvants and cytokines, thereby facilitating targeted immunomodulation.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Wang and colleagues report that cancer-cell-derived extracellular vesicles that contain miR-122 reprogram glucose metabolism of premetastatic niche cells to alter nutrient availability and promote metastasis.

JAK2 phosphorylates H3-Y41 residues to exclude the heterochromatin factor HP1α from chromatin. JAK2 is found to be required for maintenance of mouse embryonic stem cells through its action on the Nanog promoter. A mutant form of JAK2 associated with a myeloproliferative disorder allows embryonic stem cells to self renew in absence of cytokines.

Irwin McLean and colleagues report that heterozygous loss-of-function mutations in AAGAB, which encodes a cytosolic protein implicated in vesicular trafficking, cause punctate palmoplantar keratoderma. They further show that knockdown of AAGAB in keratinocytes leads to increased cell proliferation accompanied by highly elevated levels of epidermal growth factor receptor.

Snellings et al. show that an identical PIK3CA mutation is found in both developmental venous anomalies (DVAs) and associated cerebral cavernous malformations (CCMs). However, an activating MAP3K3 mutation appears only in CCMs, supporting a mechanism where DVAs develop as the result of a PIK3CA mutation.

The expression of the stimulator of interferon genes (STING) in liver tissues is associated with the progression of human nonalcoholic fatty liver disease. Specifically, STING-expressing macrophages, in particular, monocyte-derived macrophages, are positively correlated with the degree of liver inflammation and/or fibrosis progression, which appeared to be mediated by the activation of the STING-TBK1 signaling pathway in macrophage.

A strategy to enhance antigen immunogenicity is shown using polyethyleneimine adsorbed on mesoporous silica microrod vaccine as a platform for neoantigens, supporting potent humoral immune response and inhibition of tumour growth following vaccination.