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Secure and effective gene delivery system of plasmid DNA coated by polynucleotide


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Title: Secure and effective gene delivery system of plasmid DNA coated by polynucleotide
Authors: Kodama, Yukinobu / Ohkubo, Chikako / Kurosaki, Tomoaki / Egashira, Kanoko / Sato, Kayoko / Fumoto, Shintaro / Nishida, Koyo / Higuchi, Norihide / Kitahara, Takashi / Nakamura, Tadahiro / Sasaki, Hitoshi
Issue Date: 1-Jan-2015
Publisher: Informa Healthcare
Citation: Journal of Drug Targeting, 23(1), pp.43-51; 2015
Abstract: Polynucleotides are anionic macromolecules which are expected to transfer into the targeted cells through specific uptake mechanisms. So, we developed polynucleotides coating complexes of plasmid DNA (pDNA) and polyethylenimine (PEI) for a secure and efficient gene delivery system and evaluated their usefulness. Polyadenylic acid (polyA), polyuridylic acid (polyU), polycytidylic acid (polyC), and polyguanylic acid (polyG) were examined as the coating materials. pDNA/PEI/polyA, pDNA/PEI/polyU, and pDNA/PEI/polyC complexes formed nanoparticles with a negative surface charge although pDNA/PEI/polyG was aggregated. The pDNA/PEI/polyC complex showed high transgene efficiency in B16-F10 cells although there was little efficiency in pDNA/PEI/polyA and pDNA/PEI/polyU complexes. An inhibition study strongly indicated the specific uptake mechanism of pDNA/PEI/polyC complex. Polynucleotide coating complexes had lower cytotoxicity than pDNA/PEI complex. The pDNA/PEI/polyC complex showed high gene expression selectively in the spleen after intravenous injection into mice. The pDNA/PEI/polyC complex showed no agglutination with erythrocytes and no acute toxicity although these were observed in pDNA/PEI complex. Thus, we developed polynucleotide coating complexes as novel vectors for clinical gene therapy, and the pDNA/PEI/polyC complex as a useful candidate for a gene delivery system.
Keywords: Gene delivery / PDNA / Polyethylenimine / Polynucleotide / Ternary complex
URI: http://hdl.handle.net/10069/35033
ISSN: 1061186X
DOI: 10.3109/1061186X.2014.950665
Rights: © Informa Healthcare
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/35033

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