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新型异官能团交联剂的设计合成及其在基因载体中的应用

时间:2021-01-31 10:41来源:毕业论文
设计并合成了两种小分子量的PEI衍生物(L-DET-PEI 和 L-TAD-PEI)。PEI衍生物具有把质粒DNA压缩成纳米粒子的能力。凝胶阻滞分析表明质粒DNA完全被包裹时其聚合物/pDNA(w/w)的比率超过3

摘要聚乙烯亚胺(PEI)已被广泛研究用于基因的转运。但是它缺乏可降解的连接键而且细胞毒性很大,限制了其在基因治疗的应用。因此,低分子量的PEI已经被探索用作25 kDa 的PEI的替代物。为了减少毒性和提高转染效率,本论文中主要设计并合成了两种小分子量的PEI衍生物(L-DET-PEI 和 L-TAD-PEI)。PEI衍生物具有把质粒DNA压缩成纳米粒子的能力。凝胶阻滞分析表明质粒DNA完全被包裹时其聚合物/pDNA(w/w)的比率超过3。聚合物/质粒DNA复合物的颗粒大小在100纳米到200纳米之间时,适合被细胞内吞。荧光素酶的活性实验和荧光激活细胞分选术实验证实聚合物/质粒DNA复合物在多种细胞系中的转染效率高于市售25 kDa PEI, 此外在相同浓度2个细胞系中,本文中合成的聚合物与25 kDa PEI相比表现出显著的低细胞毒性,结果表明:在基因治疗中,L-TAD-PEI将极有可能成为安全而高效的基因运载体。62950

关键词   基因治疗  聚乙烯亚胺   转染效率  可降解   细胞毒性

Title  Different functional groups of the crosslinking agent novel design, synthesis and Application of gene carrier     

Abstract Polyethylenimine (PEI) has been widely studied for delivery of gene. However, it lacks degradable linkages and is too toxic for gene therapeutic applications. Hence, low-molecular-weight PEI has been explored as an alternative to PEI 25 kDa. To reduce cytotoxicity and increase transfection efficiency, we designed and synthesized two novel small-molecular-weight PEI derivatives (L-DET-PEI and L-TAD-PEI). The PEI derivative carried the ability to condense plasmid DNA (pDNA) into nanoparticles. Gel retardation assay showed complete condensation of pDNA at w/w ratios that exceeded three. The particle size of polymer/pDNA complexes was between 100 nm and 200 nm , which were appropriate for cell endocytosis. The transfection efficiency of polymer/pDNA complexes as determined with the luciferase activity assay as well as fluorescence-activated cell-sorting analysis (FACS) was higher than commercially available PEI 25 kDa .Also, the polymer exhibited signifi¬cantly lower cytotoxicity compared to PEI 25 kDa at the same concentration in two cell lines. Therefore, our results indicated that the L-TAD-PEI would be a promising candidate for safe and efficient gene delivery in gene therapy.

Keywords   gene therapy, polyethylenimine(PEI), transfection efficiency,  degradable,  cytotoxicity  

毕业论文毕业设计说明书(论文)外文摘要 

1  引言 1

1.1  基因治疗概况 1

     1.1.1  简介 1

     1.1.2  基因治疗常用方法策略 1

1.1.3  基因治疗面临的挑战 2

1.2  用于转染的基因运载体 3

     1.2.1  病毒载体 3

     1.2.2  非病毒载体 3

1.3  常用的非病毒型载体 3

     1.3.1  树枝状聚合物 4

     1.3.2  壳聚糖 5

1.3.3  脂质体 5

1.3.4  聚乙烯亚胺 6

1.4  阳离子聚合物载体的转染效率 7

1.5  阳离子聚合物载体的毒性 新型异官能团交联剂的设计合成及其在基因载体中的应用:http://www.751com.cn/yixue/lunwen_69291.html

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