RESUMO
siRNA therapeutics allows precise regulation of disease specific gene expression to treat various diseases. Although gene silencing approaches using siRNA therapeutics shows some promising results in the treatment of gene-related diseases, the practical applications has been limited by problems such as inefficient in vivo delivery to target cells and nonspecific immune responses after systemic or local administration. To overcome these issues, various in vivo delivery platforms have been introduced. Here we provide an overview for three different platform technologies for the in vivo delivery of therapeutic siRNAs (siRNA-GalNAc conjugate, SAMiRNA technology, and LNP-based delivery method) and their applications in the treatment of various diseases. In addition, a brief introduction to some rare diseases and mechanisms of siRNA therapeutics-mediated treatment is described.
Assuntos
Ensaios Clínicos como Assunto/métodos , Técnicas de Transferência de Genes , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/uso terapêutico , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacocinéticaRESUMO
Phosphorus release and uptake in a sequencing batch reactor were monitored by the simple online measurements of electric conductivity (EC) and oxidation-reduction potential (ORP), and the result was verified by the measurement of phosphate concentration changes. The influence of nitrate ion presence on the phosphorus removal was evaluated by a jar test operated in the cyclic anaerobic (anoxic)-aerobic condition. The relationships of EC, ORP and metal species with phosphorus concentrations were investigated. Under strict anaerobic conditions, EC showed positive correlation with phosphorus concentrations, but it became negligible under anoxic conditions with nitrate present. Strong inverse correlation was found between ORP values and phosphorus concentration. The increase and decrease of magnesium and potassium ions took place in accordance with phosphorus release and uptake, and the relationship between the metal species and phosphorus changes was clearer in the anaerobic condition than anoxic condition.
Assuntos
Fósforo/análise , Poluentes Químicos da Água/análise , Purificação da Água , Anaerobiose , Reatores Biológicos , Condutividade Elétrica , Nitratos/química , Nitratos/metabolismo , Oxirredução , Fósforo/isolamento & purificação , Fósforo/metabolismo , Fatores de Tempo , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodosRESUMO
Transgenic suspension cells of Oryza sativa L. cv. Dongjin utilized as a host for producing recombinant human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) were preserved in liquid nitrogen (-196 degrees C) after slow prefreezing in a deep freezer (-70 degrees C). The development of an optimal procedure for long-term storage was investigated by the addition of various concentrations of cryoprotectant mixture and osmoticum in preculture media before cooling. A pre-deep-freezing time of 120 min was the most effective for maintaining cell viability. Compared with mannitol, sorbitol, trehalose, and NaCl under the same osmotic conditions, 0.5 M sucrose was found to be the best osmoticum for preculture media. The cryoprotectant comprising sucrose, glycerol, and dimethylsulfoxide (DMSO) was applied to the precultured cells, and a combination of 1 M sucrose, 1 M glycerol, and 1 M DMSO provided the best result. The viability with this optimized condition was 88% after cryocell-banking for 1 day. The expression of hCTLA4Ig in recovered callus from cryopreservation was also kept stable, and the production level was similar to that observed in noncryopreserved cultures.
