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Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers
새로운 유전자 전달체로서의 생분해성 폴리에칠렌이민과 폴리에칠렌 글리콜 교대공중합체의 연구

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Authors
박미란
Advisor
조종수
Issue Date
2005
Publisher
서울대학교 대학원
Keywords
폴리에칠렌이민 (PEI)Polyethylenimine생분해성Degradable유전자 전달Gene delivery폴리에칠렌글리콜 (PEG)Poly(ethylene glycol)
Description
Thesis(master`s)--서울대학교 대학원 :농생명공학부,2005.
Abstract
An ideal gene carrier requires both safety and transfection effciency.
Polyethylenimine (PEI) is a well-known cationic polymer which has high
transfection efficiency owing to its buffering capacity. But it has been
reported that the PEI is cytotoxic in many cell lines and non-degradable. In
this study, we synthesized degradable PEI-alt-poly(ethylene glycol) (PEG)
copolymers using Michael-type addition reaction as a new gene carrier and
characterized them. The copolymers were complexed with plasmid DNA and the
resulting complexes were characterized by dynamic light scattering, gel
retardation and atomic force microscopy to determine the particle sizes, complex
formation and shape of complex, respectively. Cytotoxicity and transfection
efficiency of the copolymers were also checked in cultured HeLa human cervix
epithelial carcinoma cells, HepG2 human hepatoblastoma cell line and MG63 human
osteosarcoma cells. The composition of PEG to PEI in the copolymers was around 1
and the molecular weight of the copolymer was from around 8000 to 12900. The
copolymers degraded rapidly at 37¡É in 0.1M phosphate buffered saline (PBS; pH
7.4). The complete copolymer/DNA complex was formed at the N/P ratio of 12 and
the complex to DNase I resistance was obtained. The particle sizes decreased
with an increase of N/P ratio, molecular weight of PEG and had a minimum value
around 75nm at the N/P ratio of 45 in the PEI-alt-PEG(700). Cytotoxicity study
showed that the copolymers had no cytotoxic effects on cells even at high
concentration of copolymers. Also, transfection efficiency was influenced by
molecular weight of PEG, and in case of PEI-alt-PEG(258), the transfection
efficiency was higher than PEI 25K in HepG2 and MG63 whereas it was lower than
PEI 25K in HeLa. Furthermore, in vivo transfection, PEI-alt-PEG(258) mediate
gene expression 10- to 100-fold more efficient in lung and liver than PEI 25K in
both of intravenous and aerosol administration.
Language
English
URI
http://dcollection.snu.ac.kr:80/jsp/common/DcLoOrgPer.jsp?sItemId=000000051526

https://hdl.handle.net/10371/67562
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College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Food and Animal Biotechnology (식품·동물생명공학부)Theses (Master's Degree_식품·동물생명공학부)
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