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dc.contributor.author田竣元en_US
dc.contributor.authorJiun-Yuan Tianen_US
dc.contributor.author廖光文en_US
dc.contributor.authorKuang-Wen Liaoen_US
dc.date.accessioned2014-12-12T02:58:06Z-
dc.date.available2014-12-12T02:58:06Z-
dc.date.issued2006en_US
dc.identifier.urihttp://140.113.39.130/cdrfb3/record/nctu/#GT009329503en_US
dc.identifier.urihttp://hdl.handle.net/11536/79355-
dc.description.abstract重組腺相關病毒(Recombinant Adeno-associated virus, rAAV)具有許多基因治療上的優點,因此成為近來最常被研究的基因治療載體之ㄧ。此一基因治療載體由兩個部份所構成:1)由六十個病毒蛋結構蛋白 (VP1-3) 組裝的蛋白質外殼2)包裹攜帶治療用基因的單股DNA。重組腺相關病毒感染宿主細胞,主要是利用其病毒結構蛋白上的Heparin binding site與宿主細胞表面受器HSPG黏附,經由內吞作用 (endocytosis) 被帶到細胞內部並由運輸系統將其送至細胞核,完成整個感染的流程。在整個感染過程中,病毒結構蛋白上的Heparin binding site擔任與細胞交互作用的窗口,扮演影響感染細胞種類的關鍵角色。 我們的實驗目的就是修飾重組腺相關病毒的病毒結構蛋白上的Heparin binding site,使得重組腺相關病毒可以專一性的傳遞治療用基因到適當的細胞組織中。因為病毒結構蛋白上的Heparin binding site可與細胞表面接受器HSPG黏附,導致重組腺相關病毒廣泛的感染人類細胞,因此我們在不改變病毒外殼結構的情況下,將Heparin binding site做突變,使其失去與細胞表面接受器HSPG黏附的能力,解決病毒廣泛感染人類細胞的問題。在導引重組腺相關病毒到特定種類的細胞中,我們在病毒已突變的Heparin binding site嵌入由phage display所篩選出的細胞專一性胜肽,引導病毒專一性的將治療用基因送到目標細胞中。此一系統的建立,提供一個利用嵌入細胞專一性胜肽而改變重組腺病毒相關病毒感染趨性的平台,提升基因治療的效率。zh_TW
dc.description.abstractRecombinant Adeno-associated virus (rAAV) is one of the most commonly used vectors in markets. It is composed of two components, 1) a capsid with 60 viral protein subunits (VP1-3), and 2) encapsulated single-stranded DNA that carries therapeutic genes. rAAV infects its host by its binding of heparin-binding site on VPs to the HSPG on the host surface. The virus is then rapidly internalized and carried to the nucleus by the intracellular trafficking system, completing its infection cycle. Therefore, during infection, heparin-binding site serves as a key role in the cross talk between rAAV and its host. Our purpose is to modify the heparin-binding sites on the VPs of rAAV so that it can specifically bind to the target cells that we desire. Because the heparin-binding sites on rAAV can bind to the HSPG on human cells, we mutated heparin-binding sites to damage its binding capability to human HSPG. without a conformational change in the VP1-3. Then, a specific peptide selected by the phage display system was inserted into the heparin-binding sites, leading the viruses to a specific target for gene therapy. By the inserting a peptide specific to a certain tissue and mutating the heparin-binding sites, we have successfully created a platform to raise the efficiency of gene therapy.en_US
dc.language.isozh_TWen_US
dc.subject腺相關病毒zh_TW
dc.subjectAAVen_US
dc.subjectadeno-associated virusen_US
dc.title藉由修飾腺相關病毒VP1-3建立胜肽導引式基因傳遞系統zh_TW
dc.titleEstablishment of peptide-directed gene delivery system by modifying VP1-3 of AAVen_US
dc.typeThesisen_US
dc.contributor.department分子醫學與生物工程研究所zh_TW
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