DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Park, Tae-Gwan | - |
dc.contributor.advisor | 박태관 | - |
dc.contributor.author | Lee, Soo-Hyeon | - |
dc.contributor.author | 이수현 | - |
dc.date.accessioned | 2011-12-12T07:56:28Z | - |
dc.date.available | 2011-12-12T07:56:28Z | - |
dc.date.issued | 2011 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=466368&flag=dissertation | - |
dc.identifier.uri | http://hdl.handle.net/10203/27722 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명과학과, 2011.2, [ xiii, 117 p. ] | - |
dc.description.abstract | With high specificity and efficiency in target gene inhibition, small interfering RNAs (siRNAs) are promising tool for genomic therapeutics. To develop a siRNA delivery system with low cytotoxicity and high transfection efficiency, we prepared polyelectrolyte complex micelles (PECMs) of siRNA conjugated to poly(ethylene glycol) via a disulfide linkage (siRNA-PEG) using three kinds of condensing agents: amine-functionalized gold nanoparticles, cationic fusogenic peptide, Pluronic/poly(ethylenimine) nanocapsules. Gold nanoparticles chemically modified with primary amine groups could form stable polyelectrolyte complexes through electrostatic interactions with negatively charged siRNA-PEG conjugates having a cleavable di-sulfide linkage under reductive cytosol condition. The resultant core/shell type polyelectrolyte complexes surrounded by a protective PEG shell layer had a well dispersed nanostructure with a hydrodynamic diameter of 96.3 ± 25.9 nm, as determined by dynamic light scattering and transmission electron microscopy. Confocal laser scanning microscopy revealed that the nanosized polyelectrolyte complexes were efficiently internalized in human prostate carcinoma cells (PC-3 cells), and thus enhanced intracellular uptake of siRNA. Furthermore, the siRNA/gold complexes significantly inhibited the expression of a target gene within the cells without showing severe cytotoxicity. The current study demonstrated that positively charged gold nanoparticles could be potentially applied for intracellular delivery of siRNA. Anionic siRNA-PEG conjugate and cationic KALA spontaneously formed nano-sized PECMs (< 200 nm) that have an inner core of charge neutralized siRNA/KALA complex surrounded by a PEG corona. VEGF siRNA was used to demonstrate VEGF sequence-specific gene inhibition in PC-3 cells. The extent of gene silencing was gradually increased with increasing nitrogen to phosphate (N/P) ratio and the concentration of siRNA-PEG/KALA PECMs. These results suggest t... | eng |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | gene silencing | - |
dc.subject | intracellular delivery | - |
dc.subject | conjugates | - |
dc.subject | siRNA | - |
dc.subject | cancer therapy | - |
dc.subject | 암치료 | - |
dc.subject | 유전자 저해 | - |
dc.subject | 세포 내 전달 | - |
dc.subject | 접합체 | - |
dc.subject | 소간섭 알엔에이 | - |
dc.title | Gene delivery system based on siRNA conjugates | - |
dc.title.alternative | 소간섭 알엔에이 접합체를 이용한 유전자 전달 시스템 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 466368/325007 | - |
dc.description.department | 한국과학기술원 : 생명과학과, | - |
dc.identifier.uid | 020068026 | - |
dc.contributor.localauthor | Park, Tae-Gwan | - |
dc.contributor.localauthor | 박태관 | - |
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