Poly-l-glutamic acid derivatives as vectors for gene therapy

Dekie, Luc; Toncheva, Veska; Dubruel, Peter; Schacht, Etienne; Barrett, Lee; Seymour, Leonard W.

doi:10.1016/s0168-3659(99)00235-7

Cited by 131 publications

(83 citation statements)

References 22 publications

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“…A wide variety of polycationic gene carriers have been investigated. A few representative polymers include polyethylenimine (PEI), 7 poly-L-lysine, 8 polyamidoamine dendrimers, 9,10 polyiminocarbonate-containing cyclodextrin, 11 poly[a-(4-aminobutyl)-L-glycolic acid], 12 polyphosphoesters, [13][14][15] cationic derivatives of polymethacrylate and poly-L-glutamic acid, 16 gelatin and chitosan. 17 Several recent studies have shown that related cationic polymers with small structural changes result in a significant difference in transfection efficiency.…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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

Wang

Gao

Pc³

et al. 2004

Gene Ther

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“…The change in the surface charge from positive to negative must decrease the interaction of complexes with the cellular surface. It was also reported that cationic polyplexes and lipoplexes often caused agglutination of erythrocytes and albumin because of their strong electrostatic interaction -14 - [8,9]. These agglutinations often lead to rapid elimination and adverse effects, such as embolism and inflammatory reaction [28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

“…These cationic complexes, however, have been reported to show cytotoxicity and agglutination by their strong cationic surface charge [8,9].…”

Section: Introductionmentioning

confidence: 99%

γ-Polyglutamic acid-coated vectors for effective and safe gene therapy

Kurosaki

Kitahara

Kawakami

et al. 2010

Journal of Controlled Release

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“…Cytotoxicity of Chitosan and aminated Chitosan was measured using mouse fibroblasts with the direct connect method and the data are shown in Several authors have discussed the role of amine substitute on polymers in influencing toxicity. Dekie et al (43) noted that the presence of primary amines in poly(L-glutamic acid) (PGA) derivatives has a significant toxic effect on red blood cells. Based on studies with modified poly(L-lysin) (PLL), Ferruti et al, (44) conclude that polymers with tertiary amine groups exhibit a lower toxicity than those with primary and secondary residues.…”

Section: Cytotoxicitymentioning

confidence: 99%