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麻风分枝杆菌 HSP65 在烟草中的表达及其作为佐剂性关节炎口服治疗药物的效果。

Expression of Mycobacterium leprae HSP65 in tobacco and its effectiveness as an oral treatment in adjuvant-induced arthritis.

机构信息

Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B1, Francisco J Mújica S/N Col. Felicitas del Rio, CP 58060, Morelia, Michoacán, Mexico.

出版信息

Transgenic Res. 2011 Apr;20(2):221-9. doi: 10.1007/s11248-010-9404-7. Epub 2010 Jun 6.

DOI:10.1007/s11248-010-9404-7
PMID:20526808
Abstract

Transgenic plants are able to express molecules with antigenic properties. In recent years, this has led the pharmaceutical industry to use plants as alternative systems for the production of recombinant proteins. Plant-produced recombinant proteins can have important applications in therapeutics, such as in the treatment of rheumatoid arthritis (RA). In this study, the mycobacterial HSP65 protein expressed in tobacco plants was found to be effective as a treatment for adjuvant-induced arthritis (AIA). We cloned the hsp65 gene from Mycobacterium leprae into plasmid pCAMBIA 2301 under the control of the double 35S promoter from cauliflower mosaic virus. Agrobacterium tumefaciens bearing the pChsp65 plasmid was used to transform tobacco plants. Incorporation of the hsp65 gene was confirmed by PCR, reverse transcription-PCR, histochemistry, and western blot analyses in several transgenic lines of tobacco plants. Oral treatment of AIA rats with the HSP65 protein allowed them to recover body weight and joint inflammation was reduced. Our results suggest a synergistic effect between the HSP65 expressed protein and metabolites presents in tobacco plants.

摘要

转基因植物能够表达具有抗原特性的分子。近年来,这促使制药行业将植物作为生产重组蛋白的替代系统。植物生产的重组蛋白在治疗学上可能具有重要应用,例如治疗类风湿关节炎 (RA)。在这项研究中,在烟草植物中表达的分枝杆菌 HSP65 蛋白被发现可有效治疗佐剂诱导性关节炎 (AIA)。我们从麻风分枝杆菌中克隆了 hsp65 基因,使其在花椰菜花叶病毒的双 35S 启动子的控制下在质粒 pCAMBIA 2301 中表达。携带 pChsp65 质粒的根癌农杆菌被用于转化烟草植物。通过 PCR、逆转录-PCR、组织化学和 Western blot 分析,在烟草植物的几个转基因系中证实了 hsp65 基因的整合。用 HSP65 蛋白对 AIA 大鼠进行口服治疗,使其体重恢复,关节炎症减轻。我们的结果表明,表达的 HSP65 蛋白与烟草植物中存在的代谢物之间存在协同作用。

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Protective efficacy of different strategies employing Mycobacterium leprae heat-shock protein 65 against tuberculosis.采用麻风分枝杆菌热休克蛋白65的不同策略对结核病的保护效力。
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Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes.通过单次鼻内给予与阳离子脂质体复合的DNA-hsp65疫苗预防结核病。
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Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck.DNA-hsp65免疫疗法用于晚期头颈部鳞状细胞癌的I期试验。
Cancer Gene Ther. 2008 Oct;15(10):676-84. doi: 10.1038/cgt.2008.35. Epub 2008 Jun 6.
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Cost-effective production of a vaginal protein microbicide to prevent HIV transmission.以具有成本效益的方式生产一种用于预防艾滋病毒传播的阴道蛋白质杀菌剂。
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