Gene Transfer into the Lung by Nanoparticle Dextran-Spermine/Plasmid DNA Complexes

被引:32
作者
Abdullah, Syahril [1 ,2 ]
Wendy-Yeo, Wai Yeng [1 ,2 ]
Hosseinkhani, Hossein [3 ,4 ]
Hosseinkhani, Mohsen [5 ]
Masrawa, Ehab [6 ]
Ramasamy, Rajesh [1 ,7 ]
Rosli, Rozita [1 ,2 ]
Rahman, Sabariah A. [1 ,7 ]
Domb, Abraham J. [6 ]
机构
[1] Univ Putra Malaysia, MAKNA Canc Res Lab, Inst Biosci, Upm Serdang 43400, Selangor, Malaysia
[2] Univ Putra Malaysia, Med Genet Lab, Fac Med & Hlth Sci, Upm Serdang 43400, Selangor, Malaysia
[3] MIT, Ctr Biomed Engn, Cambridge, MA 02139 USA
[4] Tokyo Womens Med Univ, Int Res Inst Integrated Med Sci IREIIMS, Tokyo 1628666, Japan
[5] Tufts Univ, Sch Med, Ctr Canc Syst Biol, Caritas St Elizabeths Med Ctr, Medford, MA 02135 USA
[6] Hebrew Univ Jerusalem, Sch Pharm, Hadassah Med Sch, Dept Med Chem & Nat Prod, IL-91120 Jerusalem, Israel
[7] Univ Putra Malaysia, Dept Pathol, Fac Med & Hlth Sci, Upm Serdang 43400, Selangor, Malaysia
来源
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY | 2010年
关键词
MESENCHYMAL STEM-CELLS; IN-VITRO; PLASMID DNA; TRANSGENE EXPRESSION; CATIONIZED DEXTRAN; NONVIRAL VECTORS; CYSTIC-FIBROSIS; DELIVERY; VIVO; EFFICIENT;
D O I
10.1155/2010/284840
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A novel cationic polymer, dextran-spermine (D-SPM), has been found to mediate gene expression in a wide variety of cell lines and in vivo through systemic delivery. Here, we extended the observations by determining the optimal conditions for gene expression of D-SPM/plasmid DNA (D-SPM/pDNA) in cell lines and in the lungs of BALB/c mice via instillation delivery. In vitro studies showed that D-SPM could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency at D-SPM to pDNA weight-mixing ratio of 12. In the lungs of mice, the levels of gene expression generated by D-SPM/pDNA are highly dependent on the weight-mixing ratio of D-SPM to pDNA, amount of pDNA in the complex, and the assay time postdelivery. Readministration of the complex at day 1 following the first dosing showed no significant effect on the retention and duration of gene expression. The study also showed that there was a clear trend of increasing size of the complexes as the amount of pDNA was increased, where the sizes of the D-SPM/pDNA complexes were within the nanometer range.
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页数:10
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