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.

引用

页数：10

共 57 条

[41] Promoter attenuation in gene therapy: Interferon-gamma and tumor necrosis factor-alpha inhibit transgene expression [J].