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Conference Paper: Development of novel crosslinked poly(ethylenimine) as potential gene transfer agent

TitleDevelopment of novel crosslinked poly(ethylenimine) as potential gene transfer agent
Authors
Issue Date2008
PublisherMary Ann Liebert, Inc. Publishers
Citation
XVIth Annual Congress of the European Society of Gene and Cell Therapy, Brugge, Belgium, 13-16 November 2008. In Human Gene Therapy, 2008, v. 19 n. 10, p. 1156-1157 How to Cite?
AbstractBackground: Poly(ethylenimine) (PEI) has been considered as a potential gene delivery agent, however, it suffers from high cytotoxicity and poor in vivo transfection efficacy. Many researchers focused on giving PEI new features such as conjugating targeting ligands or crosslinking low molecular weight PEI (Mw 800, Mw 1300 and Mw 2000) or oligomeric PEI (Mn 423) by degradable disulphide bonds or ester bonds. However, the size or carbon numbers in the crosslinkers were arbitrary. Little is known in relating size or carbon number in crosslinkers respect to transfection efficacy and cytotoxicity. Methods: We hypothesize that optimizing the crosslinker size, hydrophobicity and charge density of PEI may result in reduced cytotoxicity, increased transfection efficiency and improved biocompatibility. We have designed and synthesized a series of crosslinked polymer for gene delivery by conjugating PEI Mw 800 to a biocompatible linker. The amide bonds of the crosslinked polymer were susceptible to be degraded slowly by hydrolysis and the degraded products are then readily removed from body. Results: The crosslinked PEI were tested for transfection efficacies in mammalian cell lines. Plasmid DNA encoding Enhanced Green Fluorescence Protein (EGFP) was used as a reporter gene. The protein expression was examined by fluorescence microscope. Cyctotoxicities of the crosslinked PEI were determined by MTT assay. These crosslinked PEI have higher in vitro transfection efficacies but reduced cytoxicities as compared to PEIw 25k in 293A, U373, U87, B16 and HepG2. Conclusion: Further optimizations of these crosslinked PEI should provide a better non-viral vector for gene delivery system.
Persistent Identifierhttp://hdl.handle.net/10722/61651
ISSN
2015 Impact Factor: 4.062
2015 SCImago Journal Rankings: 1.687

 

DC FieldValueLanguage
dc.contributor.authorSiu, KSen_HK
dc.contributor.authorLin, MCen_HK
dc.date.accessioned2010-07-13T03:44:23Z-
dc.date.available2010-07-13T03:44:23Z-
dc.date.issued2008en_HK
dc.identifier.citationXVIth Annual Congress of the European Society of Gene and Cell Therapy, Brugge, Belgium, 13-16 November 2008. In Human Gene Therapy, 2008, v. 19 n. 10, p. 1156-1157en_HK
dc.identifier.issn1043-0342-
dc.identifier.urihttp://hdl.handle.net/10722/61651-
dc.description.abstractBackground: Poly(ethylenimine) (PEI) has been considered as a potential gene delivery agent, however, it suffers from high cytotoxicity and poor in vivo transfection efficacy. Many researchers focused on giving PEI new features such as conjugating targeting ligands or crosslinking low molecular weight PEI (Mw 800, Mw 1300 and Mw 2000) or oligomeric PEI (Mn 423) by degradable disulphide bonds or ester bonds. However, the size or carbon numbers in the crosslinkers were arbitrary. Little is known in relating size or carbon number in crosslinkers respect to transfection efficacy and cytotoxicity. Methods: We hypothesize that optimizing the crosslinker size, hydrophobicity and charge density of PEI may result in reduced cytotoxicity, increased transfection efficiency and improved biocompatibility. We have designed and synthesized a series of crosslinked polymer for gene delivery by conjugating PEI Mw 800 to a biocompatible linker. The amide bonds of the crosslinked polymer were susceptible to be degraded slowly by hydrolysis and the degraded products are then readily removed from body. Results: The crosslinked PEI were tested for transfection efficacies in mammalian cell lines. Plasmid DNA encoding Enhanced Green Fluorescence Protein (EGFP) was used as a reporter gene. The protein expression was examined by fluorescence microscope. Cyctotoxicities of the crosslinked PEI were determined by MTT assay. These crosslinked PEI have higher in vitro transfection efficacies but reduced cytoxicities as compared to PEIw 25k in 293A, U373, U87, B16 and HepG2. Conclusion: Further optimizations of these crosslinked PEI should provide a better non-viral vector for gene delivery system.-
dc.languageengen_HK
dc.publisherMary Ann Liebert, Inc. Publishers-
dc.relation.ispartofHuman Gene Therapy-
dc.titleDevelopment of novel crosslinked poly(ethylenimine) as potential gene transfer agenten_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLin, MC: mcllin@HKUCC.hku.hken_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1089/hum.2008.1034-
dc.identifier.hkuros153369en_HK

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