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首页> 外文期刊>Langenbeck's archives of surgery >Prolongation of heart allograft survival after long-term expression of soluble MHC class I antigens and vIL-10 in the liver by AAV-plasmid-mediated gene transfer.
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Prolongation of heart allograft survival after long-term expression of soluble MHC class I antigens and vIL-10 in the liver by AAV-plasmid-mediated gene transfer.

机译:通过AAV质粒介导的基因转移在肝脏中长期表达可溶性I类MHC抗原和vIL-10后,心脏移植的存活时间延长。

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INTRODUCTION: The essential prerequisite for successful gene therapy in vivo is an effective and long-lasting transfer of the desired gene into the respective cell type or tissue. Over the last decades, many different methods have been developed for this purpose. The use of plasmid DNA seems to be a good alternative to the commonly used viral vectors because its large-scale production is simple, and side effects are low. Unfortunately, most reports describe only short-term expression in vivo, probably due to the lack of genomic integration in the target cell. This problem can possibly be addressed by the use of adeno-associated virus plasmids (AAV plasmids), where the coding sequences are cloned between the AAV-specific inverted terminal repeats. Here, we report our results after allogeneic heart transplantation, which followed AAV-plasmid-mediated gene transfer of the rat soluble major histocompatibility complex class I antigen RT1.A(a) and viral interleukin (vIL)-10 in the "high"-responder Dark Agouti to Lewis rat strain combination. RESULTS: A high and stable long-term expression was achieved by in vivo transfection of the liver using AAV plasmids. Serum levels over 1,000 ng/ml of soluble RT1.A(a) and over 300 pg of vIL-10, respectively, were achieved. Expression levels remained high for up to several months. A mean prolongation of heart allograft survival of 1 to 2 days was demonstrated after transfection of either RT1.A(a) or vIL-10.
机译:简介:成功进行体内基因治疗的必要前提是将所需基因有效且持久地转移到各自的细胞类型或组织中。在过去的几十年中,为此目的开发了许多不同的方法。质粒DNA的使用似乎是常用病毒载体的良好替代品,因为其大规模生产简单且副作用低。不幸的是,大多数报道仅描述了体内的短期表达,这可能是由于靶细胞中缺乏基因组整合。可以通过使用腺相关病毒质粒(AAV质粒)解决此问题,其中将编码序列克隆在AAV特异性反向末端重复序列之间。在这里,我们报告同种异体心脏移植后的结果,这是在AAV质粒介导的大鼠可溶性主要组织相容性复合体I类抗原RT1.A(a)和病毒白介素(vIL)-10在“高”-响应者Dark Agouti对Lewis大鼠品系的组合。结果:通过使用AAV质粒体内转染肝脏可实现长期稳定的高表达。血清水平分别超过1,000 ng / ml的可溶性RT1.A(a)和300 pg以上的vIL-10。表达水平持续长达数月之久。 RT1.A(a)或vIL-10转染后,心脏同种异体移植平均存活时间延长了1至2天。

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