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Conference Paper: Development of novel crosslinked poly(ethylenimine) as potential gene transfer agent
Title | Development of novel crosslinked poly(ethylenimine) as potential gene transfer agent |
---|---|
Authors | |
Issue Date | 2008 |
Publisher | Mary 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? |
Abstract | Background: 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 Identifier | http://hdl.handle.net/10722/61651 |
ISSN | 2023 Impact Factor: 3.9 2023 SCImago Journal Rankings: 1.091 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Siu, KS | en_HK |
dc.contributor.author | Lin, MC | en_HK |
dc.date.accessioned | 2010-07-13T03:44:23Z | - |
dc.date.available | 2010-07-13T03:44:23Z | - |
dc.date.issued | 2008 | en_HK |
dc.identifier.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 | en_HK |
dc.identifier.issn | 1043-0342 | - |
dc.identifier.uri | http://hdl.handle.net/10722/61651 | - |
dc.description.abstract | Background: 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.language | eng | en_HK |
dc.publisher | Mary Ann Liebert, Inc. Publishers | - |
dc.relation.ispartof | Human Gene Therapy | - |
dc.title | Development of novel crosslinked poly(ethylenimine) as potential gene transfer agent | en_HK |
dc.type | Conference_Paper | en_HK |
dc.identifier.email | Lin, MC: mcllin@HKUCC.hku.hk | en_HK |
dc.identifier.authority | Lin, MC=rp00746 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1089/hum.2008.1034 | - |
dc.identifier.scopus | eid_2-s2.0-85018896286 | - |
dc.identifier.hkuros | 153369 | en_HK |
dc.identifier.issnl | 1043-0342 | - |