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971.
Transduction of modified factor VIII gene improves lentiviral gene therapy efficacy for hemophilia A
Jie Gong Tsai-Hua Chung Jie Zheng Huyong Zheng Lung-Ji Chang 《The Journal of biological chemistry》2021,297(6)
Hemophilia A (HA) is a bleeding disorder caused by deficiency of the coagulation factor VIII (F8). F8 replacement is standard of care, whereas gene therapy (F8 gene) for HA is an attractive investigational approach. However, the large size of the F8 gene and the immunogenicity of the product present challenges in development of the F8 gene therapy. To resolve these problems, we synthesized a shortened F8 gene (F8-BDD) and cloned it into a lentiviral vector (LV). The F8-BDD produced mainly short cleaved inactive products in LV-transduced cells. To improve F8 functionality, we designed two novel F8-BDD genes, one with an insertion of eight specific N-glycosylation sites (F8-N8) and another which restored all N-glycosylation sites (F8-299) in the B domain. Although the overall protein expression was reduced, high coagulation activity (>100-fold) was detected in the supernatants of LV-F8-N8- and LV-F8-299-transduced cells. Protein analysis of F8 and the procoagulation cofactor, von Willebrand Factor, showed enhanced interaction after restoration of B domain glycosylation using F8-299. HA mouse hematopoietic stem cell transplantation studies illustrated that the bleeding phenotype was corrected after LV-F8-N8 or -299 gene transfer into the hematopoietic stem cells. Importantly, the F8-299 modification markedly reduced immunogenicity of the F8 protein in these HA mice. In conclusion, the modified F8-299 gene could be efficiently packaged into LV and, although with reduced expression, produced highly stable and functional F8 protein that corrected the bleeding phenotype without inhibitory immunogenicity. We anticipate that these results will be beneficial in the development of gene therapies against HA. 相似文献
972.
Zhen Kang Wenwen Ding Xu Gong Qingtao Liu Guocheng Du Jian Chen 《World journal of microbiology & biotechnology》2017,33(11):200
5-Aminolevulinic acid (5-ALA) is the precursor for the biosynthesis of tetrapyrrole compounds and has broad applications in the medical and agricultural fields. Because of the disadvantages of chemical synthesis methods, microbial production of 5-ALA has drawn intensive attention and has been regarded as an alternative in the last years, especially with the rapid development of metabolic engineering and synthetic biology. In this mini-review, recent advances on the application and microbial production of 5-ALA using novel biological approaches (such as whole-cell enzymatic-transformation, metabolic pathway engineering and cell-free process) are described and discussed in detail. In addition, the challenges and prospects of synthetic biology are discussed. 相似文献
973.
There is a global consensus on the fact that human activities are increasingly eroding biodiversity, especially in many ecologically rich regions of the world. Quantifying these biodiversity losses over large administrative areas, along with the impacts of the respective driving factors is necessary for biodiversity conservation. In this study, we used readily available spatial data on infrastructure, fragmentation, and land use together with ecological data on terrestrial arthropods (as species surrogate) to carry out spatial assessment and mapping of biodiversity values in the Western Region of Ghana, a highly degraded part of the West African biodiversity hotspot. Compared with its pristine condition, our results show that the region has a remaining mean species abundance (MSA) of approximately 52%, indicating a loss of 48% due to anthropogenic activities (mainly cocoa and oil palm farming). Areas of national protection (i.e. national parks and forest reserves) did not prove to have much promise for biodiversity conservation in the region since many were found to have low MSA values. Moreover, according to our arthropod data, no areas of high MSA values were found outside protected areas. However, because the thick, continuous, structurally complex canopies of these orchards responsible for the biodiversity loss provide natural connectivity between protected reserves, diversification of understory vegetation and a reduction in the use of agrochemicals particularly weedicides and pesticides may yield significant conservation outcomes. 相似文献
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976.
Dan Du Tao Jin Rui Zhang Liqiang Hu Zhihua Xing Na Shi Yan Shen Meng Gong 《Bioorganic & medicinal chemistry letters》2017,27(6):1467-1470
One new bibenzyl (1) and one new phenanthrene (2), together with two known bibenzyls (3–4) and four known diarylheptanoids (5–8) were isolated from the rhizomes of Dioscorea zingiberensis. The structures of 1–2 were elucidated by spectroscopic methods including 1D and 2D NMR. Phenols 1–8 were evaluated for their anti-pancreatitic activities on sodium taurocholate (NaT)-induced pancreatic acinars necrosis. Notably, 0.5 mM of compound 6 exhibited comparable inhibitory effect with 5 mM of caffeine. Furthermore, compound 6 prevented the ATP depletion and excessive ROS production which could be also involved in mitochondria-mediated injuries in acute pancreatitis. As a result, compound 6 has been demonstrated to be a potential candidate for mediating mitochondrial dysfunction to prevent pancreatic necrosis. This study is also the first report on the isolation of bibenzyls and diarylheptanoids from this plant. 相似文献
977.
Xiaoqing Sun Zexin Hong Moyi Liu Su Guo Di Yang Yong Wang Tian Lan Linyu Gao Hongxia Qi Ping Gong Yajing Liu 《Bioorganic & medicinal chemistry》2017,25(10):2800-2810
A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b, 15c, 20b, 20c, and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c, with an IC50 (FXa) value of 0.14 μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor. 相似文献
978.
Can Yuan Wenjuan Zhong Fangsheng Mou Yiyun Gong Deqiang Pu Peicheng Ji Haiyan Huang Zehu Yang Chao Zhang 《Physiology and Molecular Biology of Plants》2017,23(1):35-41
Chloroplast genome sequences are very useful for species identification and phylogenetics. Chuanminshen (Chuanminshen violaceum Sheh et Shan) is an important traditional Chinese medicinal plant, for which the phylogenetic position is still controversial. In this study, the complete chloroplast genome of Chuanminshen violaceum Sheh et Shan was determined. The total size of Chuanminshen chloroplast genome was 154,529 bp with 37.8% GC content. It has the typical quadripartite structure, a large single copy (17,800 bp) and a small single copy (84,171 bp) and a pair of inverted repeats (26,279 bp). The whole genome harbors 132 genes, which includes 85 protein coding genes, 37 tRNA genes, eight rRNA genes, and two pseudogenes. Thirty-nine SSR loci, 32 tandem repeats and 49 dispersed repeats were found. Phylogenetic analyses results with the help of MEGA showed a new insight for the Chuanminshen phylogenetic relationship with the reported chloroplast genomes in Apiales plants. 相似文献
979.
Han?Y.?Gong Yang?Li Gen?Fang Dao?H.?Hu Zhao?H.?Wang Guang?H.?Yu Yang?S.?LiEmail author 《Plant Molecular Biology Reporter》2017,35(6):619-633
Two cyanobacterial genes ccaA and FBP/SBPase related to CO2 hydration and Calvin cycle were induced into rice plants. Three homologous transgenic strains were generated with ccaA and FBP/SBPase alone or in combination independently and grown under field conditions. The biochemical, physiological, and leaf anatomic results indicated that stomatal and mesophyll conductance to CO2, net photosynthetic rate, carboxylation efficiency, and other physiological and biochemical parameters increased significantly in the overexpression strains with FBP/SBPase and CcaA + FBP/SBPase but not in the CcaA strain. Leaf anatomy structure showed no significant modifications between the transgenic and wild-type strains. The CcaA protein was shown to be located in the cytoplasm. These results showed that the effect on improving photosynthetic capacity by FBP/SBPase was better than by CcaA, and only when CcaA was co-transformed with FBP/SBPase was the synergistic effect observed. The multigene-stacking approaches and their synergistic action for improving the photosynthetic capacity in rice are discussed. 相似文献
980.
Haipeng Gong 《Proteins》2017,85(12):2162-2169
Helix‐helix interactions are crucial in the structure assembly, stability and function of helix‐rich proteins including many membrane proteins. In spite of remarkable progresses over the past decades, the accuracy of predicting protein structures from their amino acid sequences is still far from satisfaction. In this work, we focused on a simpler problem, the prediction of helix‐helix interactions, the results of which could facilitate practical protein structure prediction by constraining the sampling space. Specifically, we started from the noisy 2D residue contact maps derived from correlated residue mutations, and utilized ridge detection to identify the characteristic residue contact patterns for helix‐helix interactions. The ridge information as well as a few additional features were then fed into a machine learning model HHConPred to predict interactions between helix pairs. In an independent test, our method achieved an F‐measure of ~60% for predicting helix‐helix interactions. Moreover, although the model was trained mainly using soluble proteins, it could be extended to membrane proteins with at least comparable performance relatively to previous approaches that were generated purely using membrane proteins. All data and source codes are available at http://166.111.152.91/Downloads.html or https://github.com/dpxiong/HHConPred . 相似文献