Search results for "Stability."
showing 10 items of 3015 documents
Determinants of intracellular RNA pharmacokinetics: Implications for RNA-based immunotherapeutics
2011
RNAs with optimized properties are increasingly investigated as a tool to deliver the genetic information of complete antigens into professional antigen-presenting dendritic cells for HLA haplotype-independent antigen-specific vaccination against cancer. As the dose of the antigen and duration of its presentation are critical factors for generating strong and sustained antigen-specific immune responses, improvement of the immunobioavailability of RNA-based vaccines has been a recurrent subject of research. Substantial increase of the amount of antigen produced from RNA can be achieved by optimizing RNA stability and translational efficiency. Both features are determined by cis-acting elemen…
Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids
2005
Dietary vegetable oils and fish oils rich in PUFA (polyunsaturated fatty acids) exert hypocholesterolaemic and hypotriglyceridaemic effects in rodents. The plasma cholesterol-lowering properties of PUFA are due partly to a diminution of cholesterol synthesis and of the activity of the rate-limiting enzyme HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase). To better understand the mechanisms involved, we examined how tuna fish oil and individual n−3 and n−6 PUFA affect the expression of hepatic FPP synthase (farnesyl diphosphate synthase), a SREBP (sterol regulatory element-binding protein) target enzyme that is subject to negative-feedback regulation by sterols, in co-ordination …
mRNA as a versatile tool for exogenous protein expression.
2012
Several viral and non-viral vectors have been developed for exogenous protein expression in specific cells. Conventionally, this purpose is achieved through the use of recombinant DNA. But mainly due to the risks associated with permanent genetic alteration of cells, safety and ethical concerns have been raised for the use of DNA-based vectors in human clinical therapy. In the last years, synthetic messenger RNA has emerged as powerful tool to deliver genetic information. RNA vectors exhibit several advantages compared to DNA and are particularly interesting for applications that require transient gene expression. RNA stability and translation efficiency can be increased by cis-acting struc…
Synthetic mRNAs with Superior Translation and Stability Properties
2012
The translational efficiency and stability of synthetic mRNA in both cultured cells and whole animals can be improved by incorporation of modified cap structures at the 5'-end. mRNAs are synthesized in vitro by a phage RNA polymerase transcribing a plasmid containing the mRNA sequence in the presence of all four NTPs plus a cap dinucleotide. Modifications in the cap dinucleotide at the 2'- or 3'-positions of m(7)Guo, or modifications in the polyphosphate chain, can improve both translational efficiency and stability of the mRNA, thereby increasing the amount and duration of protein expression. In the context of RNA-based immunotherapy, the latter is especially important for antigen producti…
Pre-Analytical Determination of the Effect of Extended Warm or Cold Ischaemia on RNA Stability in the Human Ileum Mucosa
2015
The use of banked human tissue, obtained with informed consent after elective surgical procedures, represents a powerful model for understanding underlying mechanisms of diseases or therapeutic interventions and for establishing prognostic markers. However, donated tissues typically have varying times of warm ischaemia in situ due to blood arrest or cold ischaemia due to procurement and transportation. Hence, before using these tissues, it is important to carry out pre-analytical studies to ensure that they are representative of the in vivo state. In particular, tissues of the gastrointestinal tract have been thought to have low RNA stability. Therefore, this study aimed to determine if ext…
Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune r…
2010
Vaccination with in vitro transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen in vivo. By analyzing the effect of different synthetic 5' mRNA cap analogs on the kinetics of the encoded protein, we found that m(2)(7,2'-O)Gpp(S)pG (beta-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover, in vivo delivery of the antigen as beta-S-ARCA(D1)-c…
Abscisic Acid Connects Phytohormone Signaling with RNA Metabolic Pathways and Promotes an Antiviral Response that Is Evaded by a Self-Controlled RNA …
2020
© 2020 The Authors.
Characterization of LiF and CaF2 surfaces using MIES and UPS (HeI)
1998
Metastable impact electron spectroscopy (MIES) and UPS (HeI) in combination with ab initio calculations (CRYSTALcode) were applied to study surface and bulk defects in LiF and CaF2. The investigated stoichiometric, defective and doped surfaces are LiF, LiF doped with Mg, and CaF2. The experimental information obtained on the electronic structure of stoichiometric and defective surfaces of LiF (100), LiF on W (110) and CaF2 (111) is discussed on the basis of the ab initio calculations. MIES spectra show features from Li agglomerates on the surface of electron bombarded LiF. The electronic structure of the LiF:Mg single crystal shows additional features above the valence band maximum caused b…
The energy transfer to the luminescence centers in PbWO4
1998
Abstract The luminescence spectra, rise and decay kinetics and the yield of luminescence in undoped PbWO 4 crystals were studied after pulsed electron beam irradiation. The luminescence intensity rise observed after irradiation pulse showed two mechanisms—excitonic relaxation and electron–hole recombination—were involved in the formation of the excited states of the blue luminescence centers. It is proposed that the excited states of WO 3 and WO 2− 4 luminescence centers were formed from some intermediate metastable state.
X-ray emitting MHD accretion shocks in classical T Tauri stars. Case for moderate to high plasma-beta values
2009
AIMS. We investigate the stability and dynamics of accretion shocks in CTTSs, considering the case of beta >= 1 in the post-shock region. In these cases the 1D approximation is not valid and a multi-dimensional MHD approach is necessary. METHODS. We model an accretion stream propagating through the atmosphere of a CTTS and impacting onto its chromosphere, by performing 2D axisymmetric MHD simulations. The model takes into account the stellar magnetic field, the gravity, the radiative cooling, and the thermal conduction (including the effects of heat flux saturation). RESULTS. The dynamics and stability of the accretion shock strongly depends on the plasma beta. In the case of shocks with…