小干预RNA对人乳头瘤病毒6bE7基因表达的干预作用
发布时间:2019-03-03 11:41
【摘要】:人类乳头瘤病毒(Human Papilloma Virus,HPV)感染引起的传染性皮肤粘膜疣状增生、性传播性疾病以及恶性肿瘤是全世界范围内的常见病和多发病。我国最常见的性传播性疾病尖锐湿疣(Condyloma acuminatum,CA)即由HPV感染引起,主要是6和11型。临床上顽固难治,复发率高。目前CA的主要治疗方法有物理、药物疗法(包括手术、激光、冷冻、足叶草脂、抗病毒药、腐蚀剂或消毒剂、抗癌药等)和免疫疗法等。物理疗法和药物局部疗法对肉眼可见瘤体的疗效较好,但无法消除HPV感染的亚临床状态,很难起到根治CA的效果。因此至今仍然缺乏理想的防治手段。寻求理想的治疗和预防手段是我国控制尖锐湿疣的关键。 最近发现的小干预RNA(short or small interfering RNA,siRNA)对同源mRNA的转录后水平的表达抑制作用使寻求有效控制尖锐湿疣等HPV感染手段的人们看到了一片曙光。长为19-23个碱基的双链核甘酸通过细胞内的RNA诱导的沉默复合物(RNA-induced silencing complex,RISC)有效地降解内源mRNA,干扰了靶基因的转录表达,这种小RNA分子即为siRNA,这种现象称为RNA干预(RNA interference,RNAi)。利用这种现象抑制某些特定基因表达来作为研究基因功能或阻断感染病原体复制的手段即小RNA干预技术。 本研究将尖锐湿疣主要病原体HPV6b型的早期基因E7作为靶基因,研究其同源siRNA(包括双链siRNA和shRNA表达质粒)在体外实验和动物实验中对HPV6bE7表达的抑制作用以及对HPV感染的阻断作用,有利于促进RNA干预技术在尖锐湿疣等HPV感染相关疾病治疗中的应用。
[Abstract]:Verrucous hyperplasia of infectious skin mucosa caused by human papillomavirus (Human Papilloma Virus,HPV) infection, sexually transmitted diseases and malignant tumors are common and frequently occurring diseases all over the world. Condyloma acuminatum (Condyloma acuminatum,CA), the most common sexually transmitted disease in China, is caused by HPV infection, mainly 6 and 11 types. Clinically, stubborn and difficult to treat, the recurrence rate is high. At present, the main therapeutic methods of CA include physical, drug therapy (including surgery, laser, freezing, foot leaf fat, antiviral drugs, corrosion agents or disinfectants, anti-cancer drugs, etc.) and immunotherapy. Physiotherapy and local drug therapy have a good effect on visible tumors, but can not eliminate the subclinical state of HPV infection, so it is difficult to cure CA. Therefore, there is still a lack of ideal means of prevention and control. Seeking ideal treatment and prevention means is the key to control condyloma acuminatum in our country. The inhibition of the expression of homologous mRNA at the post-transcriptional level by the recently discovered small intervention RNA (short or small interfering RNA,siRNA provides a dawn for people seeking to effectively control HPV infection such as condyloma acuminatum. RNA-induced silencing complex (RNA-induced silencing complex,RISC) effectively degrades endogenous mRNA, a small RNA molecule known as siRNA, which interferes with the transcriptional expression of the target gene through a 23-base-long, double-stranded ribonucleic acid complex (RNA-induced silencing complex,RISC). This phenomenon is called RNA intervention (RNA interference,RNAi). This phenomenon is used to inhibit the expression of certain genes as a means of studying gene function or blocking the replication of infectious pathogens, that is, small RNA intervention technology. In this study, the early gene E7 of HPV6b, the main pathogen of condyloma acuminatum, was used as the target gene. To study the inhibitory effect of homologous siRNA (including double-stranded siRNA and shRNA expression plasmids) on the expression of HPV6bE7 and the blocking effect on HPV infection in vitro and in animal experiments. It is helpful to promote the application of RNA intervention technique in the treatment of HPV infection-related diseases such as condyloma acuminatum.
【学位授予单位】:浙江大学
【学位级别】:硕士
【学位授予年份】:2006
【分类号】:R752;R373
本文编号:2433664
[Abstract]:Verrucous hyperplasia of infectious skin mucosa caused by human papillomavirus (Human Papilloma Virus,HPV) infection, sexually transmitted diseases and malignant tumors are common and frequently occurring diseases all over the world. Condyloma acuminatum (Condyloma acuminatum,CA), the most common sexually transmitted disease in China, is caused by HPV infection, mainly 6 and 11 types. Clinically, stubborn and difficult to treat, the recurrence rate is high. At present, the main therapeutic methods of CA include physical, drug therapy (including surgery, laser, freezing, foot leaf fat, antiviral drugs, corrosion agents or disinfectants, anti-cancer drugs, etc.) and immunotherapy. Physiotherapy and local drug therapy have a good effect on visible tumors, but can not eliminate the subclinical state of HPV infection, so it is difficult to cure CA. Therefore, there is still a lack of ideal means of prevention and control. Seeking ideal treatment and prevention means is the key to control condyloma acuminatum in our country. The inhibition of the expression of homologous mRNA at the post-transcriptional level by the recently discovered small intervention RNA (short or small interfering RNA,siRNA provides a dawn for people seeking to effectively control HPV infection such as condyloma acuminatum. RNA-induced silencing complex (RNA-induced silencing complex,RISC) effectively degrades endogenous mRNA, a small RNA molecule known as siRNA, which interferes with the transcriptional expression of the target gene through a 23-base-long, double-stranded ribonucleic acid complex (RNA-induced silencing complex,RISC). This phenomenon is called RNA intervention (RNA interference,RNAi). This phenomenon is used to inhibit the expression of certain genes as a means of studying gene function or blocking the replication of infectious pathogens, that is, small RNA intervention technology. In this study, the early gene E7 of HPV6b, the main pathogen of condyloma acuminatum, was used as the target gene. To study the inhibitory effect of homologous siRNA (including double-stranded siRNA and shRNA expression plasmids) on the expression of HPV6bE7 and the blocking effect on HPV infection in vitro and in animal experiments. It is helpful to promote the application of RNA intervention technique in the treatment of HPV infection-related diseases such as condyloma acuminatum.
【学位授予单位】:浙江大学
【学位级别】:硕士
【学位授予年份】:2006
【分类号】:R752;R373
【引证文献】
相关硕士学位论文 前1条
1 韩志敏;人毛乳头细胞中P16基因的检测及意义[D];河北医科大学;2012年
,本文编号:2433664
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