DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Park, Tae-Gwan | - |
dc.contributor.advisor | 박태관 | - |
dc.contributor.author | Mok, Hye-Jung | - |
dc.contributor.author | 목혜정 | - |
dc.date.accessioned | 2011-12-12T07:55:20Z | - |
dc.date.available | 2011-12-12T07:55:20Z | - |
dc.date.issued | 2008 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=303575&flag=dissertation | - |
dc.identifier.uri | http://hdl.handle.net/10203/27647 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명과학과, 2008. 8., [ x, 106 p. ] | - |
dc.description.abstract | For the efficient and specific delivery of nucleic acid drugs, reducible nanoparticle systems and surface engineered nanoparticle systems were investigated. Reducible PEG nanogels via thiol-crosslinking encapsulating plasmid DNA were prepared for the specific delivery of plasmid DNA only in environmental reductive condition, such as cytoplasm. DNA was dissolved in selected organic solvents in the presence of poly(ethylene glycol) (PEG). Nano-scale PEG/DNA complex (~100 nm) was produced in dimethylsulfoxide (DMSO) phase. Using a thiol-functionalized six-arm branched PEG for DNA solubilization, the PEG/DNA nanocomplex was crosslinked through the formation of disulfide linkages between the thiol groups, resulting in the production of stable PEG/DNA nanogels in aqueous solution. DNA release from the nanogels could be modulated by changing the concentration of an external reducing agent. While the released plasmid DNA from the nanogels maintained intact structural integrity, the transfection efficiency by PEG nanogels was lower than that by conventional cationic carriers such as PEI and $lipofectamine^{TM}$. To enhance transfection efficiency, reducible polyelectrolyte nanocomplexes cleavable in reductive condition were prepared. Antisense oligodeoxynucleotide (ODN) was covalently conjugated to hyaluronic acid (HA) via a reducible di-sulfide linkage, and the HA-ODN conjugate was complexed with protamine to increase the extent of cellular uptake and enhance the gene inhibition efficiency of GFP expression. The HA-ODN conjugate formed more stable polyelectrolyte complexes with protamine as compared to naked ODN, probably due to its increased charge density. As alternative approach, self-crosslinked and reducible peptide was synthesized for stable formation of nanoscale complexes with an siRNA-PEG conjugate to enhance transfection efficiency in serum containing condition without compromising cytotoxicity. A fusogenic peptide, KALA, with two cysteine residues at bo... | eng |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | nucleic acid drug | - |
dc.subject | nanoparticle | - |
dc.subject | delivery | - |
dc.subject | targeting | - |
dc.subject | polymer | - |
dc.subject | 유전자 약물 | - |
dc.subject | 나노 입자 | - |
dc.subject | 전달 | - |
dc.subject | 타겟팅 | - |
dc.subject | 고분자 | - |
dc.subject | nucleic acid drug | - |
dc.subject | nanoparticle | - |
dc.subject | delivery | - |
dc.subject | targeting | - |
dc.subject | polymer | - |
dc.subject | 유전자 약물 | - |
dc.subject | 나노 입자 | - |
dc.subject | 전달 | - |
dc.subject | 타겟팅 | - |
dc.subject | 고분자 | - |
dc.title | Efficient intracellular delivery of nucleic acid drugs using smart polymer nanoparticles | - |
dc.title.alternative | 효과적 세포내 유전자 전달을 위한 지능형 나노 입자의 설계 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 303575/325007 | - |
dc.description.department | 한국과학기술원 : 생명과학과, | - |
dc.identifier.uid | 020045828 | - |
dc.contributor.localauthor | Park, Tae-Gwan | - |
dc.contributor.localauthor | 박태관 | - |
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