Advanced siRNA delivery systems using nanoparticles = 나노입자를 이용한 siRNA 전달에 관한 연구

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Small interfering RNA (siRNA) of about 22 nucleotides in length can degrade mRNA that shares a homologous sequence with the siRNA by the mechanism called RNA interference (RNAi), resulting in the highly specific inhibition of gene expression. Because of its high specificity and high efficiency, siRNA technology began to be widely used in biomedical research and in the development of innovative medicines. Especially, it is the one of the most attractive technologies for gene therapy of many diseases such as cancers and genetic diseases. The clinical potential of ‘Naked’ siRNA, however, is limited by the poor pharmacokinetic profiles, resulting from the susceptibility of RNA molecules to serum nuclease, renal clearance and non-specific biodistribution. Also, naked siRNA is too negatively charged to cross cellular membranes. The advanced delivery systems of siRNA, therefore, have been required. In chapter 1, branched polyethylenimine (bPEI) (Mw= 25 k) conjugated with catechol groups (PEI-C) was crosslinked to produce PEI nanogels (PCNs), which were used as a new class of small interfering RNA (siRNA) delivery carrier. The conjugated catechol groups were crosslinked with primary amines of PEI under basic conditions. The size and morphology of PCNs were analyzed by dynamic light scattering (DLS) and atomic force microscopy (AFM). The resultant PCNs were very stable and had an average diameter of $111.4 \plusmn 14.8 nm$ in aqueous solution. Compared with bPEI, PCNs exhibited far reduced cytotoxicity, and formed more stable complexes with siRNA. The PCNs/siRNA complexes exhibited enhanced cellular uptake and promoted gene silencing efficiency, suggesting that they can be potentially used as a less cytotoxic siRNA carrier. In chapter 2, thermo-responsive quantum dots (Thermo-QDs) that exhibit an “on-demand” cellular uptake behavior via selective “shielding/deshielding” of cell penetrating peptides (CPP) on the surface were fabricated. Poly(N-isopropylacrylamide) (...
Park, Tae-Gwanresearcher박태관researcher
한국과학기술원 : 생명과학과,
Issue Date
419050/325007  / 020088020

학위논문(석사) - 한국과학기술원 : 생명과학과, 2010.2, [ vii, 46 p. ]


nanoparticles; siRNA; 약물전달; Drug delivery system; 에스아이알엔에이; 나노입자

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