RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Theory for the FCC-ee : Report on the 11th FCC-ee Workshop

The Future Circular Collider (FCC) at CERN, a proposed 100-km circular facility with several colliders in succession, culminates with a 100 TeV proton-proton collider. It offers a vast new domain of exploration in particle physics, with orders of magnitude advances in terms of Precision, Sensitivity and Energy. The implementation plan foresees, as a first step, an Electroweak Factory electron-positron collider. This high luminosity facility, operating between 90 and 365 GeV centre-of-mass energy, will study the heavy particles of the Standard Model, Z, W, Higgs, and top with unprecedented accuracy. The Electroweak Factory $e^+e^-$ collider constitutes a real challenge to the theory and to precision calculations, triggering the need for the development of new mathematical methods and software tools. A first workshop in 2018 had focused on the first FCC-ee stage, the Tera-Z, and confronted the theoretical status of precision Standard Model calculations on the Z-boson resonance to the experimental demands. The second workshop in January 2019, which is reported here, extended the scope to the next stages, with the production of W-bosons (FCC-ee-W), the Higgs boson (FCC-ee-H) and top quarks (FCC-ee-tt). In particular, the theoretical precision in the determination of the crucial input parameters, alpha_QED, alpha_QCD, M_W, m_t at the level of FCC-ee requirements is thoroughly discussed. The requirements on Standard Model theory calculations were spelled out, so as to meet the demanding accuracy of the FCC-ee experimental potential. The discussion of innovative methods and tools for multi-loop calculations was deepened. Furthermore, phenomenological analyses beyond the Standard Model were discussed, in particular the effective theory approaches. The reports of 2018 and 2019 serve as white papers of the workshop results and subsequent developments