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Change in Dietary Patterns and Change in Waist Circumference and DXA Trunk Fat Among Postmenopausal Women
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The production of human glucocerebrosidase in glyco‐engineered Nicotiana benthamiana plants
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Juthamard Limkul Sayoko Iizuka Yohei Sato Ryo Misaki Takao Ohashi Toya Ohashi Kazuhito Fujiyama 《Plant biotechnology journal》2016,14(8):1682-1694
For the production of therapeutic proteins in plants, the presence of β1,2‐xylose and core α1,3‐fucose on plants’ N‐glycan structures has been debated for their antigenic activity. In this study, RNA interference (RNAi) technology was used to down‐regulate the endogenous N‐acetylglucosaminyltransferase I (GNTI) expression in Nicotiana benthamiana. One glyco‐engineered line (NbGNTI‐RNAi) showed a strong reduction of plant‐specific N‐glycans, with the result that as much as 90.9% of the total N‐glycans were of high‐mannose type. Therefore, this NbGNTI‐RNAi would be a promising system for the production of therapeutic glycoproteins in plants. The NbGNTI‐RNAi plant was cross‐pollinated with transgenic N. benthamiana expressing human glucocerebrosidase (GC). The recombinant GC, which has been used for enzyme replacement therapy in patients with Gaucher's disease, requires terminal mannose for its therapeutic efficacy. The N‐glycan structures that were presented on all of the four occupied N‐glycosylation sites of recombinant GC in NbGNTI‐RNAi plants (GCgnt1) showed that the majority (ranging from 73.3% up to 85.5%) of the N‐glycans had mannose‐type structures lacking potential immunogenic β1,2‐xylose and α1,3‐fucose epitopes. Moreover, GCgnt1 could be taken up into the macrophage cells via mannose receptors, and distributed and taken up into the liver and spleen, the target organs in the treatment of Gaucher's disease. Notably, the NbGNTI‐RNAi line, producing GC, was stable and the NbGNTI‐RNAi plants were viable and did not show any obvious phenotype. Therefore, it would provide a robust tool for the production of GC with customized N‐glycan structures. 相似文献
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A large-scale transformation procedure handling an adequate number of stable transformants with highly efficient positive-negative selection is a necessary prerequisite to successful gene targeting by homologous recombination, as the integration of a transgene by somatic homologous recombination in higher plants has been reported to be 10-3 to 10-5 compared with random integration by non-homologous end joining. We established an efficient and large-scale Agrobacterium-mediated rice transformation protocol that generated around 103 stable transformants routinely from 150 seeds and a strong positive-negative selection procedure that resulted in survivors at 10-2 using the gene for diphtheria toxin A fragment as a negative marker. The established transformation procedure provides a basis for efficient gene targeting in rice.Abbreviations
AS:
Acetosyringone
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5-FU:
5-Fluorouracil
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FW:
Fresh weight
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GT:
Gene targeting
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HR:
Homologous recombination
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NHEJ:
Non-homologous end joining
Communicated by H. Ebinuma 相似文献
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Yano S Kazuno H Sato T Suzuki N Emura T Wierzba K Yamashita J Tada Y Yamada Y Fukushima M Asao T 《Bioorganic & medicinal chemistry》2004,12(13):3443-3450
A series of novel 6-methylene-bridged uracil derivatives have been optimized for clinical use as the inhibitors of human thymidine phosphorylase (TP). We describe their synthesis and evaluation. Introduction of a guanidino or an amidino group enhanced the in vitro inhibitory activity of TP comparing with formerly reported inhibitor 1. Their selectivity for TP based on uridine phosphorylase inhibitory activity was also evaluated. Compound 2 (TPI) has been selected for clinical evaluation based on its strong TP inhibition and excellent modulation of 2'-deoxy-5-(trifluoromethyl)uridine (F(3)dThd) pharmacokinetics. As a result, TAS-102 (a combination of F(3)dThd and TPI) is currently in phase 1 clinical studies. 相似文献
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Synthesis of amide compounds of ferulic acid,and their stimulatory effects on insulin secretion in vitro 总被引:2,自引:0,他引:2
Nomura E Kashiwada A Hosoda A Nakamura K Morishita H Tsuno T Taniguchi H 《Bioorganic & medicinal chemistry》2003,11(17):3807-3813
We prepared amide compounds which were derived from ferulic acid using various amines, and investigated their stimulatory effects on insulin secretion using rat pancreatic RIN-5F cells. Most of these compounds exhibited significant promotion of the insulin-release at a concentration of 10 microM and in particular, the amides having n-butyl, n-pentyl, pyrrolidine, and piperidine groups showed high activity. 相似文献