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|Title:||New polyphosphoramidate with a spermidine side chain as a gene carrier|
|Keywords:||CNS gene delivery|
Non-viral gene delivery
|Citation:||Wang, J., Zhang, P.-C., Lu, H.-F., Ma, N., Wang, S., Mao, H.-Q., Leong, K.W. (2002-09-18). New polyphosphoramidate with a spermidine side chain as a gene carrier. Journal of Controlled Release 83 (1) : 157-168. ScholarBank@NUS Repository. https://doi.org/10.1016/S0168-3659(02)00180-3|
|Abstract:||A new cationic polymer (PPA-SP), polyphosphoramidate bearing spermidine side chain, was prepared as a non-viral vector for gene delivery. PPA-SP was synthesized from poly(1,2-propylene H-phosphonate) by the Atherton-Todd reaction. The weight average molecular weight of PPA-SP was 3.44×104 with a number average degree of polymerization of 90, as determined by GPC/LS/RI method. The average net positive charge per polymer chain was 102. PPA-SP was able to condense plasmid DNA efficiently and formed complexes at an N/P ratio (free amino groups in polymer to phosphate groups in DNA) of 2 and above, as determined by agarose gel electrophoresis. This new gene carrier offered significant protection to DNA against nuclease degradation at N/P ratios above 2, and showed lower cytotoxicity than PLL and PEI in cell culture. The LD50 of PPA-SP was 85 μg/ml in COS-7 cells, in contrast to 20 and 42 μg/ml for PLL and PEI, respectively. The complexes prepared in saline at N/P ratios of 5∼10 had an average size of 250 nm and zeta-potential of 26 mV. PPA-SP mediated efficient gene transfection in a number of cell lines, and the transfection protocol was optimized in HEK293 cells using a luciferase plasmid as a marker gene. Gene expression mediated by PPA-SP was greatly enhanced when chloroquine was used in conjunction at a concentration of 100 μM. Under the optimized condition, PPA-SP/DNA complexes yield a luciferase expression level closed to PEI/DNA complexes or Transfast mediated transfection. In a non-invasive CNS gene delivery model, PPA-SP/DNA complexes yielded comparable bcl-2 expression as PEI/DNA complexes in mouse brain stem following injection of the complexes in the tongue. © 2002 Elsevier Science B.V. All rights reserved.|
|Source Title:||Journal of Controlled Release|
|Appears in Collections:||Staff Publications|
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