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Ewing's sarcoma family tumors are dependent on an oncogenic fusion protein, most commonly EWS-FLI1, which interacts with RNA helicase A (RHA) in transcriptional complexes. Erkizan et al. have identified a small molecule that inhibits the interaction of RHA with EWS-FLI1 and impairs the growth of Ewing's sarcoma xenografts in mice. The findings provide evidence that targeting tumor-specific transcription factors may be a feasible approach to treating cancer.

Glycerol phosphate modifications of cell wall carbohydrates localize regulators of cell division in Streptococcus mutans.

Antigenic epitopes differ in their immunogenicity. Yewdell and colleagues show that B cell and antibody responses to influenza A virus infection display reproducible dynamic immunodominance hierarchies to viral hemagglutinin epitopes.

The hierarchical deconstruction of the complex pectic glycan rhamnogalacturonan-II by the human gut bacterium Bacteroides thetaiotaomicron reveals seven new families of glycoside hydrolases and three catalytic functions not previously observed.

Here the authors report an exploratory analysis of a clinical trial that tested different influenza virus vaccination platforms. The results show that multiple seasons of recombinant or cell-based influenza vaccinations may be needed to redirect antibody responses away from immune memory to egg-adapted epitopes and refocus on epitopes on the circulating viruses.

Gene regulation in engineered microbial populations is often tuned at individual cell levels. Now, a population-wide amplification system has been devised that expands the dynamic range of plasmid transfer and gene regulation in bacteria.

The immunological parameters that define severe influenza disease are not clear within human real time infections. Here the authors compare a severe influenza infection cohort with an influenza vaccinated cohort to understand correlates of severe influenza disease.

Evolution of human H3N2 influenza has limited the specificity of hemagglutinin to a subset of glycan receptors, which brings challenges. By glyco-engineering cell lines, authors show the importance of extended glycan receptors for growth of recent H3N2 viruses and relevance to their production for vaccines.

Here, the authors report the development of a genetic platform for mRNA-LNP vaccines that encodes the two major influenza virus glycoprotein genes into a single mRNA molecule. They show that this approach is generalizable to diverse influenza virus strains and is immunogenic and protective in mouse and ferret models of influenza disease.

Genetic, structural and biochemical analysis identifies GacH as a glycerol phosphate transferase that modifies N-acetylglucosamine components of group A carbohydrates (GAC) in streptococcal cell walls.

A single dose of an adeno-associated virus vector encoding an HIV-1 broadly neutralizing antibody given shortly after birth results in persistent antibody expression and protection from infection in rhesus macaque models of human HIV-1 transmission through breastfeeding and sexual intercourse.

RAG2-SCID is a primary immunodeficiency caused by mutations in Recombination-activating gene 2 (RAG2). Here the authors report a RAG2 correction strategy that replaces the entire endogenous coding sequence (CDS) to maintain the endogenous spatiotemporal gene regulation and locus architecture.

In a small trial of patients with severe systemic lupus erythematosus and nephritis, treatment with allogeneic T cells with a CD19 chimeric antigen receptor inserted into the T cell receptor locus and deletion of the PD-1 (PDCD1) gene were safe and associated with reduced disease activity.

QS-21—an FDA-approved vaccine adjuvant—and several structural analogues of QS-21 can be synthesized in engineered yeast strains, and this process is much less laborious compared with the conventional mode of extraction from the Chilean soapbark tree.

The initiation of translation in eukaryotes can be impeded by secondary structures in the mRNA upstream of the initiation codon. There is increasing evidence that several helicases act in concert to overcome such structures and to promote processive movement of the 40S ribosome subunit.

Cell cycle arrest after DNA damage is achieved by the expression of the CDK inhibitor p21. Here the authors show that spontaneous DNA damage incurred in unperturbed cell cycles, leads to cell populations exhibiting a bistable state, with p53 and p21 regulating the proliferation-quiescence decision.

A bacterial screen yields a Cas9 variant that retains high on-target activity when delivered in the RNP format. As proof of principle, this Cas9 variant enables high-level correction of the sickle cell disease mutation in patient-derived HSPCs.

Pulendran and colleagues define a molecular signature that can be used to predict the durability of antibody responses to vaccination and reveal important insights into the mechanisms by which vaccines induce durable immunity.

A sunflower pan-genome determined by sequencing about 500 accessions, including wild, landrace and cultivated lines, showed that introgression from the wild species has profoundly shaped the cultivar gene pool and contributed disease resistance genes.

Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.

Current methods for auto-transfusion often result in disturbances to the patient’s blood homeostasis, leading to an increased bleeding risk. Here, the authors develop heparin-mimicking self-anticoagulant sponges for safe and convenient whole blood auto-transfusion, and study underlying mechanisms.

Glycosyl phosphosaccharides represent a large and important family of complex glycans, but are difficult to synthesize efficiently. Here, the authors disclose a stereoselective methodology to make α-glycosyl phosphosaccharides, via gold(I)-catalyzed glycosylation of phosphoric acid acceptors.

Engineered switchgrass and poplar are better feedstocks for biofuel synthesis and yield more biomass in multi-year field trials.

In this study the authors measure the concentration of 25-hydroxyvitamin D and vitamin D binding protein (DBP) in 65,589 neonatal dried blood samples. Findings from further analyses include that the genetic correlates of DBP concentration predict the risk of vitamin D deficiency.

In this study, the authors perform an interactome study of Zika virus (ZIKV) 5’UTR stem-loop B region and identify two host factors, interleukin enhancer binding factor 3 (ILF3) and DEAH-box helicase 9 (DHX9), that positively regulate antiviral RNAi to inhibit virus replication and ZIKV-induced microcephaly in vivo.

The authors present a multidisciplinary approach investigating the mechanistic underpinnings of galactan synthase 1 and use their data to propose a new model for complex pectin biosynthesis.

In this work, the authors report a three-step charge-driven coacervation model involving dynamic complexes between a positively charged IDR of human RECQ4 and G-quadruplexes. The IDR also interacts with Replication Protein A, implying RECQ4’s regulatory role.

Primary T cells with multiple genetic modifications are rapidly isolated by negative selection.

Unlike Panax species, which can produce dammarane-type saponins, Aralia elata can only synthesize oleananetype saponins. Here, the authors reveal that the loss of the dammaranediol synthase-encoding gene and tandem duplication of triterpene biosynthetic genes drive structural divergences of saponins between the two genera.

Shuman et al. report that epileptic mice harbor desynchronized hippocampal interneuron activity and unstable spatial representations, revealing that precise intrahippocampal synchronization is critical for spatial coding.

In this paper, a CRISPR-based gene addition strategy at the CX3CR1 locus of human hematopoietic stem cells is proposed to efficiently generate microglia engineered for the regulated expression of therapeutic genes for the treatment of neurodegenerative disorders.

The predominance of manufacturing process patents asserted in litigation by originator biologics companies against would-be biosimilar entrants has resulted in a number of Congressional and administrative agency proposals that could increase scrutiny and limit enforceability.