Hybrid inorganic-organic capsules for efficient intracellular delivery of novel siRNAs against influenza A (H1N1) virus infection

This work was supported by ARUK project grant 21210 ‘Sustained and Controllable Local Delivery of Anti-inflammatory Therapeutics with Nanoengineered Microcapsules’. The work was also supported in part by Russian Foundation of Basic Research grants No. 16-33-50153 mol_nr, No. 16-33-00966 mol_a, Russian Science Foundation grant No. 15-15-00170 and Russian Governmental Program ‘‘Nauka’’, No. 1.1658.2016, 4002

Degradable Polyelectrolyte Multilayers that Promote the Release of siRNA

Author Manuscript 2012 June 21We report an approach to the design of degradable polyelectrolyte-based films for the controlled release of siRNA from surfaces. Our approach is based on stepwise, layer-by-layer assembly of multilayered polyelectrolyte films (or “polyelectrolyte multilayers”, PEMs) using siRNA and a hydrolytically degradable poly(β-amino ester) (polymer 1). Fabrication of films using siRNA sequences for green fluorescent protein (GFP) or firefly luciferase resulted in linear growth of ultrathin films (~50 nm thick) that promoted the surface-mediated release of siRNA upon incubation in physiologically relevant media. Physicochemical characterization of these siRNA-containing films revealed large differences in film growth profiles, physical erosion profiles, and siRNA release profiles as compared to PEMs fabricated using polymer 1 and larger plasmid DNA constructs. For example, whereas films fabricated using plasmid DNA erode gradually and release DNA over a period of ~48 h, films fabricated using siRNA released ~65% of incorporated siRNA within the first hour of incubation, prior to the onset of any observed film erosion. This initial burst of release was followed by a second, slower phase of release (accompanied by gradual film erosion) over the next 23 h. These differences in release profiles and other behaviors likely result, at least in part, from large differences in the sizes of siRNA and plasmid DNA. Finally, we demonstrate that the siRNA in these films is released in a form that remains intact, functional, and able to silence targeted protein expression upon administration to mammalian cells in vitro. The results of this investigation provide a platform for the design of thin films and coatings that could be used to localize the release of siRNA from surfaces in a variety of fundamental and applied contexts (e.g., for development of new research tools or approaches to delivery from film-coated implants and other devices)

Precision Electroweak Measurements on the Z resonance.

We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron–positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLD experiment using a polarised beam at SLC. The measurements include cross-sections, forward–backward asymmetries and polarised asymmetries. The mass and width of the Z boson, mZ and ΓZ, and its couplings to fermions, for example the ρ parameter and the effective electroweak mixing angle for leptons, are precisely measured: The number of light neutrino species is determined to be 2.9840±0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward–backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, , and the mass of the W boson, . These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of mt and mW, the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than at 95% confidence level