Polyethylene glycol modified polyethylenimine for improved CNS gene transfer: effects of PEGylation extent

Tang, Guping; Zeng, Jieming; Gao, Shan; Ma, Yingjie; Shi, Leilei; Li, Y.; Too, Heng Phon; Wang, S.

doi:10.1016/s0142-9612(03)00029-2

Cited by 201 publications

(129 citation statements)

References 22 publications

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“…This scenario is of interest because the presence of serum better emulates in vivo conditions and has been previously shown to reduce transfection efficiency of PEI:DNA systems [36]. Consistent with previous findings, transfection efficiencies of both naked DNA and PEI:DNA complexes were reduced in presence of serum for both real and sham exposure to ultrasound (Student's t test, p < 0.001).…”

Section: Effect Of Incubation Time and Serum On Ultrasound-mediated Tsupporting

confidence: 86%

Synergistic effect of ultrasound and PEI on DNA transfection in vitro

Deshpande

Prausnitz

2007

Journal of Controlled Release

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Ultrasound and poly(ethylenimine) (PEI) have each separately been shown to increase DNA transfection efficiency. This study tested the hypothesis that the combination of ultrasound and PEI can have a synergistic effect to increase DNA transfection. This in vitro study assessed transfection efficiency of two different DNA plasmids encoding green fluorescent protein and firefly luciferase in two different cells types, a primary culture of human aortic smooth muscle cells and an immortal line of human prostrate cancer cells. We found that ultrasound sonication increased transfection up to 18-fold, DNA complexation with PEI increased transfection up to 90-fold, and the combination of ultrasound and PEI synergistically increased transfection up to 200-fold, which resulted in reporter gene expression by 34% of cells. Kinetic measurements found that the effects of ultrasound alone acted quickly, whereas increased transfection by PEI either alone or in combination with ultrasound strongly benefited from a 4-h incubation with the DNA plasmid after sonication. Although serum reduced absolute expression levels, it did not affect the relative increase in transfection when ultrasound was added to PEI enhancement. Flow cytometry measurements showed that sonication increased intracellular uptake of labelled DNA complexed to PEI by 55% relative to PEI complexation alone. Electrophoresis assay showed no damage to DNA or PEI-DNA complexes after sonication. Overall, these results suggest that the combination of ultrasound and PEI can have a synergistic effect to increase DNA transfection.

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Section: Effect Of Incubation Time and Serum On Ultrasound-mediated Tsupporting

confidence: 86%

Synergistic effect of ultrasound and PEI on DNA transfection in vitro

Deshpande

Prausnitz

2007

Journal of Controlled Release

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“…32,33 The previous study has demonstrated that PEI mediates 40-fold higher transgene expression in the spinal cord than naked plasmid DNA following intrathecal injection into the CSF. 24 However, intramuscular administration and intravenous injection of all PPA/DNA nanoparticles, including PEI/DNA particles, failed to show any significant luciferase expression in the muscle and in liver and lung, respectively.…”

Section: Discussionmentioning

confidence: 96%

“…The in vivo transfection efficiency of PPA/DNA nanoparticles was evaluated in a rat spinal cord gene expression model as reported earlier 24 following intrathecal injection of PPA/DNA nanoparticles at a charge ratio of 10 ( Figure 10). PEI/DNA nanoparticles at a charge ratio of 15 was included as a control because a previous study demonstrated the highest gene expression at this charge ratio.…”

Section: Gene Expression In Rat Spinal Cord Following Intrathecal Injmentioning

confidence: 99%

“…PEI/DNA nanoparticles at a charge ratio of 15 was included as a control because a previous study demonstrated the highest gene expression at this charge ratio. 24 A plasmid pCAGLuc driven by a composite promoter CAG consisting of the CMV IE Nanoparticles equivalent to 4 mg of pDNA were given to each rat. Transgene expression was analyzed 48 h after injection.…”

Section: Gene Expression In Rat Spinal Cord Following Intrathecal Injmentioning

confidence: 99%

“…The previous study showed that gene expression mediated by PEI was detected in spinal parenchyma and meninges, and spread over the whole spinal cord with slightly higher expression levels in the lumbar and thoracic regions. 24 In this study, we analyzed the transgene expression in the whole spinal cord (Figure 10).…”

Section: Gene Expression In Rat Spinal Cord Following Intrathecal Injmentioning

confidence: 99%

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Polyphosphoramidate gene carriers: effect of charge group on gene transfer efficiency

Wang

Gao

Pc³

et al. 2004

Gene Ther

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Cationic polymeric carriers have been widely used for gene delivery. However, the structure-function relationship, especially the effect of charge groups of cationic polymeric carriers on the transfection activity, is poorly understood. To examine this important parameter, a series of cationic polymers, polyphosphoramidates (PPAs) with an identical backbone, same side chain spacer, similar molecular weights but different charge groups containing primary to quaternary amino groups (PPA-EA, PPA-MEA, PPA-DMA and PPA-TMA, Figure 1) were synthesized. The DNAbinding affinity of these four PPAs increased in the order of PPA-EAoPPA-MEAoPPA-DMABPPA-TMA. The cytotoxicity decreased in the order of PPA-EA4PPA-MEA4PPA-DMA4PPA-TMA. Particle size and zeta potential of four different types of PPA/DNA nanoparticles did not show significant correlation with PPA structure. These PPAs did not show significant buffering capacity within pH 5-7, even though transfection mediated by PPA-EA was the only one that seemed to be limited by endolysomal escape. Endocytosis of DNA mediated by PPAs was also similar (17-22%) for all four PPAs. However, the transfection efficiency of these PPAs varied significantly. In vitro transfection efficiency of PPAs decreased in the order of PPA-EA4PPA-MEA4PPA-DMABPPA-TMA. Nanoparticles with PPA-EA containing primary amino groups gave the highest transfection efficiency in cell lines at the charge ratios from 6/1 to 20/1 ( þ /À). Matching the trend of transfection efficiency observed in vitro, PPA-EA mediated the highest transgene expression, comparable to that of polyethylenimine, in the spinal cord following intrathecal injection of the nanoparticles. These results establish that PPA gene carriers with primary amino group side chains are more potent than those with secondary, tertiary or quaternary amino groups in vitro and in the intrathecal gene delivery model.

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Biological and Medical Applications of Hyperbranched Polymers

Smet

2011

Hyperbranched Polymers

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Polyethylene glycol modified polyethylenimine for improved CNS gene transfer: effects of PEGylation extent

Cited by 201 publications

References 22 publications

Synergistic effect of ultrasound and PEI on DNA transfection in vitro

Synergistic effect of ultrasound and PEI on DNA transfection in vitro

Polyphosphoramidate gene carriers: effect of charge group on gene transfer efficiency

Biological and Medical Applications of Hyperbranched Polymers

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