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乙型肝炎作为一种发病率高、死亡率高的传染性疾病,已严重威胁人类健康,乙肝病毒(hepatitis B virus,HBV)是诱发乙型肝炎的重要病因。目前,最主要的治疗方法是运用抗病毒药物控制病情,但这些药物都不能完全治愈乙型肝炎且复发率高。近年来,RNA干扰技术(RNA interference, RNAi)逐渐成为有效、快速治疗乙型肝炎的新疗法。利用RNA干扰技术体外合成针对HBV基因的siRNA,选择适当的载体将其运送至靶细胞,使HBV基因沉默,从而抑制病毒复制,可有效达到治疗乙肝的效果。本文围绕siRNA沉默HBV基因的设计原理、递送载体、靶向策略、以及治疗效果与应用前景等方面进行了系统综述,为今后siRNA治疗乙肝的临床应用提供参考。 相似文献
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RNA干扰技术在哺乳动物中的应用 总被引:12,自引:0,他引:12
RNA干扰(RNAi)是生物界普遍存在的一种抵御外来基因和病毒感染的进化保守机制.RNAi是由双链RNA触发的转录后基因沉默机制,具有序列特异性,在哺乳动物细胞中,RNAi由21~23个核苷酸组成的双链RNA引发.小干扰RNA(siRNA)可以在体外合成或通过表达载体在哺乳动物细胞内合成.由于RNAi技术具有快速、简单和特异性强等特点,在基因功能研究、抗病毒治疗和抗肿瘤治疗等方面有广泛的应用前景. 相似文献
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黄渊余 《生物化学与生物物理进展》2019,46(3):313-322
近期,RNA干扰(RNAi)制药公司Alnylam开发的小干扰RNA (siRNA)药物ONPATTRO?美国食品与药物管理局和欧盟委员会批准上市,用于治疗成人患者的遗传性转甲状腺素蛋白淀粉样变性引起的多发性神经病变.这是全球第一款RNAi药物,该事件标志着人类继小分子化合物、单克隆抗体蛋白类药物后,在前沿生物制药领域实现了新的突破,意味着RNAi疗法从基础研究到临床治疗的开发全过程首次贯通,具有里程碑式的意义.本文概述了该药物及适应症的基本情况,介绍了RNAi发现历史、作用机理与药物特征,RNAi药物的研发历程,以及该领域关键技术的最新研究进展. 相似文献
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抗病毒作用是RNA干扰(RNAi)在植物及低等动物中的一个重要功能。一方面,宿主细胞编码并表达短干扰RNA(siRNA),对入侵细胞的病毒产生抑制作用;另一方面,病毒编码并表达特定的RNA或蛋白质,以对抗宿主细胞的RNAi。在部分脊椎动物病毒中已经发现多种由病毒编码的微RNA(miRNA),它们对病毒及细胞基因的表达有重要的调节作用。同时,某些细胞miRNA也可影响脊椎动物病毒的复制。然而,RNAi在脊椎动物细胞中是否具有广谱抗病毒活性、脊椎动物病毒又是否普遍编码miRNA及普遍具备拮抗RNAi的机制?目前尚无定论,有待于进一步的研究加以阐明。 相似文献
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RNAi是由双链RNA(dsRNA)所诱发的转录后水平上的基因沉默.由于对靶基因沉默作用的高度特异性和高效性,因此近年来用于肿瘤性疾病、感染性疾病、遗传性疾病等疾病的基因治疗研究,特别是在抗病毒领域的研究更是成为其应用热点之一.虽然目前RNAi已经较为广泛地应用于动物病毒及各种疾病病毒的基因治疗研究中,但其在应用过程中还有许多亟待解决的问题.本文就RNAi及其在抗病毒领域的应用研究和其存在的问题展开综述. 相似文献
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Negative HBcAg in immunohistochemistry assay of liver biopsy is a predictive factor for the treatment of patients with nucleos(t)ide analogue therapy 下载免费PDF全文
Mingxing Huang Jian Liu Monica Chow Xuan Zhou Zongping Han Zhenjian He Jinfang Xue Zhe Zhu Xinhua Li Jinyu Xia 《Journal of cellular and molecular medicine》2018,22(3):1675-1683
The hepatitis B core antigen (HBcAg) is an important target for antiviral response in chronic hepatitis B (CHB) patients. However, the correlation between HBcAg in the hepatocyte nucleus and nucleos(t)ide analogue (NA) therapeutic response is unclear. We sought to evaluate the role of HBcAg by analysing liver biopsies for viral response in NA‐naïve hepatitis B e antigen (HBeAg) positive (+) CHB patients via immunohistochemistry (IHC). A total of 48 HBcAg‐negative (?) patients and 48 HBcAg (+) patients with matching baseline characteristics were retrospectively analysed for up to 288 weeks. Virological response (VR) rates of patients in the HBcAg (?) group were significantly higher at week 48 and 96 than the HBcAg (+) group (77.1% versus 45.8% at week 48, respectively, P = 0.002 and 95.3% versus 83.3% at week 96, respectively, P = 0.045). The serological negative conversion rate of HBeAg was significantly higher in the HBcAg (?) than in the HBcAg (+) group from week 96 to 288 (35.4 % versus 14.6% at week 96, respectively, P = 0.018; 60.4% versus 14.6%, respectively, P < 0.001 at week 144; 72.9% versus 35.4%, respectively, P < 0.001 at week 288). The cumulative frequencies of VR and lack of HBeAg were higher in the HBcAg (?) group (both P < 0.05). Binary logistic regression analysis showed that HBcAg (?) was the predictor for the lack of HBeAg (OR 4.482, 95% CI: 1.58–12.68). In summary, the absence of HBcAg in the hepatocyte nucleus could be an independent predictor for HBeAg seroconversion rates during NA‐naïve treatment in HBeAg (+) CHB patients. 相似文献
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Samantha Therezinha Almeida Pereira Leite Marilene Borges da Silva Marco Andrey Pepato Francisco José Dutra Souto Raquel Alves dos Santos Carmen Lucia Bassi-Branco 《Memórias do Instituto Oswaldo Cruz》2014,109(1):15-20
In this study, we analysed the frequency of micronuclei (MN), nucleoplasmic bridges
(NPBs) and nuclear buds (NBUDs) and evaluated mutagen-induced sensitivity in the
lymphocytes of patients chronically infected with hepatitis B virus (HBV) or
hepatitis C virus (HCV). In total, 49 patients with chronic viral hepatitis (28
HBV-infected and 21 HCV-infected patients) and 33 healthy, non-infected blood donor
controls were investigated. The frequencies (‰) of MN, NPBs and NBUDs in the controls
were 4.41 ± 2.15, 1.15 ± 0.97 and 2.98 ± 1.31, respectively. The frequencies of MN
and NPBs were significantly increased (p < 0.0001) in the patient group (7.01 ±
3.23 and 2.76 ± 2.08, respectively) compared with the control group. When considered
separately, the HBV-infected patients (7.18 ± 3.57) and HCV-infected patients (3.27 ±
2.40) each had greater numbers of MN than did the controls (p < 0.0001). The
HCV-infected patients displayed high numbers of NPBs (2.09 ± 1.33) and NBUDs (4.38 ±
3.28), but only the HBV-infected patients exhibited a significant difference (NPBs =
3.27 ± 2.40, p < 0.0001 and NBUDs = 4.71 ± 2.79, p = 0.03) in comparison with the
controls. Similar results were obtained for males, but not for females, when all
patients or the HBV-infected group was compared with the controls. The lymphocytes of
the infected patients did not exhibit sensitivity to mutagen in comparison with the
lymphocytes of the controls (p = 0.06). These results showed that the lymphocytes of
patients who were chronically infected with HBV or HCV presented greater chromosomal
instability. 相似文献
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本文用ELISA间接法检测急性和慢性乙型肝炎病人血清特异性抗HBcIgG,用ELISA捕捉法检测特异性抗HBcIgM。11例急性乙肝病人急性期抗HBcIgM100%阳性,抗HBcIgG全部阴性;恢复期抗HBcIgM 81.8%阴转,抗HBcIgG则100%阳转。17例慢性乙肝病人抗HBcIgM82.35%阳性,抗HBcIgG 100%阳性。被检血清经密度梯度超速离心,证实抗HBcIgM和抗HBcIgG两类抗体反应在急性和慢性乙肝病人血清中具有不同的动态规律。 相似文献
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为获得更快速的免疫应答,用30μg/ml乙肝血源疫苗以0、2、6周免疫程序对68名HBsAg阳性母亲婴儿作了阻断HBV母婴传播免疫效果的观察,并和常规的0、1、6月接种方案的结果进行了比较。结果表明HBIG合并乙肝疫苗或单用疫苗组产生抗─HBs(>10mIU/ml)血清转换率于T6M、T12M时分别为91.89%,和83.87%;81.08%和83.87%。短程和常规免疫方案婴儿所产生的保护性抗─HBS动态比较,表明以0、2、6周免疫后的T6w、T6m时的抗─HBs有效率分别为19.35%和83.87%,明显高于0、1、6月免疫者同期抗体水平(P<0.01)。至T12M时两组的阳转率无显著性差异,说明0、2、6周免疫方案能早期诱导出保护性抗─HBs免疫应答。 相似文献
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Neysi Ibarra Abel Caballero Ernesto Gonzlez Rodolfo Valds 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,735(2):314
An immunoaffinity chromatographic method was developed using a mAb immunosorbent to purify recombinant hepatitis B surface antigen (r-HBsAg) from yeast. Elution conditions using a mAb-coated ELISA were improved to select the best conditions to purify r-HBsAg. The optimum results in terms of total quantitative recovery were obtained using 20 mM Tris pH 11.6. An increase in the CB.Hep-1 mAb (anti-HBsAg) useful immunosorbents half-life and in its yield per cycle was obtained when alkaline elution conditions were used. Moreover, the basic conditions do not affect either the antigenic characteristics or the purity or the molecular integrity of r-HBsAg. 相似文献
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Ina Schulte E-juan Zhang Zhong-ji Meng Rong-juan Pei Mengji Lu Michael Roggendorf 《中国病毒学》2008,23(2):107-115
The woodchuck model is an excellent animal model to study hepadnaviral infection. The new progresses in this model made possible to examine the T-cell mediated immune responses in acute and chronic hepadnaviral infection. Recently, a new assay for cytotoxic T-cells based on detection of CD107 was established for the woodchuck model. In addition, new immunotherapeutic approaches based on combination of potent antiviral treatment and DNA-protein vaccines were proven to be useful for treatment of chronic hepatitis B. 相似文献
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掌握百色市乙型肝炎疫苗纳入儿童免疫规划后的免疫效果,客观评价免疫规划工作现状。方法按现况研究原理,全市12个县(区),每个县(区)各抽取150名儿童,每个县在东、西、南、北、中五个方位随机抽取5个行政村,每个行政村抽取6个年龄组(1~6岁儿童),每个年龄组抽取5名常住儿童(当地居住三个月以上),收集血清样本进行乙肝病毒感染相关标志表面抗原及抗体检测。结果全市共调查1~6岁儿童1 809名儿童,乙肝表面抗原携带率为0.66%,低于2006年全国调查的1~4岁人群乙肝表面抗原携带率(0.96%),达到中国《2006—2010年全国乙型病毒性肝炎防治规划》提出的5岁以下儿童乙肝表面抗原携带率<1%的控制目标要求;1~6岁儿童乙肝表面抗体阳性率为77.77%,高于2006年全国调查的1~4岁人群乙肝抗体阳性率(71.24%)。结论百色市自2003年将乙肝疫苗纳入免疫规划管理后,乙肝免疫效果显著,乙肝病毒表面抗原阳性率大幅度下降,婴幼儿体内保护性抗体水平也高于全国水平。加强对孕产妇住院分娩率和婴幼儿乙肝疫苗接种工作,尤其是乙肝疫苗首针及时接种是今后乙肝预防控制的重点。 相似文献