Current aspects of gene therapy: implications for vascular interventions

Reifers, Frank; Kreuzer, Jörg

doi:10.1007/bf00196353

Cited by 5 publications

(3 citation statements)

References 67 publications

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“…Although various functional reporter or therapeutic genes have been introduced into cells in culture and the expression of these genes in various tissues has been shown in animal models, [1][2][3][4][5][6][7][8][9] human clinical trials have been disappointing, with only a few individual cases of success. [10][11][12][13] These results have prompted calls for more basic research on vectors and the cell biology of gene delivery.…”

Section: Introductionmentioning

confidence: 99%

Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides

et al. 1998

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Potential problems with the use of viral vectors for gene also enhanced by association with transferrin, GALA or the therapy necessitate the development of efficient nonviral influenza hemagglutinin N terminal peptide HA-2, but to a vectors. The association of transferrin, or the pH-sensitive smaller extent compared with the negatively charged compeptide GALA, with cationic liposomes composed of 1,2-plexes. The enhancement of gene delivery by transferrin dioleoyl-3-(trimethylammonium) propane and its equimolar or GALA was not affected significantly by the presence of mixture with dioleoylphosphatidylethanolamine, under conserum and did not cause significant cytotoxicity. Our ditions where the liposome/DNA complex is negatively results indicate that negatively charged ternary complexes charged, drastically increased luciferase expression from of cationic liposomes, DNA and transferrin, or fusigenic pCMVluc. The percentage of cells transfected, measured peptides, can facilitate efficient transfection of cultured by ␤-galactosidase expression, was also increased by cells, and that they may alleviate the drawbacks of the use about 10-fold. The zeta potential of the ternary complexes of highly positively charged complexes for gene delivery was lower than that of the liposome/DNA complexes.in vivo. Transfection activity of positively charged complexes was

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Section: Introductionmentioning

confidence: 99%

Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides

et al. 1998

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“…Cationica mphiphiles, also known as cationic lipids,h ave shown DNA complexation properties useful for cell transfection. [13,[36][37][38][39][40][41][42][43] Ar ecent review evidenced the great potentialo f these nonviral vectors, in particular the gemini surfactants, owing to tunability of their molecular moieties:h ydrophobic chains and hydrophilic head group, spacer,a nd counterion. [9] However,e fficient nonviral delivery systems must still be realized.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Physicochemical Characterization, and Interaction with DNA of Long‐Alkyl‐Chain Gemini Pyridinium Surfactants

et al. 2015

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Pyridinium gemini surfactants with hexadecyl chains linked to nitrogen atoms and a tuned aliphatic spacer that bridges the two pyridinium polar heads in 2,2′‐positions have been synthesized and characterized. A multitechnique approach allowed us to study the aggregation behavior, using conductivity, surface tension, and fluorescence. Graphs of the specific conductivity (κ) versus the surfactant molar concentration (C), and graphs of the molar conductivity (Λ) versus C0.5 suggest pre‐aggregation phenomena of these amphiphiles at very low concentration. The trends of Amin as a function of the spacer length confirm the hypothesis of a conformational change of the molecule with four methylene groups as spacer owing to stacking interactions between the two pyridinium rings mediated by the counterion. Moreover, the trends of Amin and counterion binding (β) suggest that the spacer must be longer than eight carbon atoms to fold efficiently toward the micellar core. The opportunity to tune the surfactant structure and aggregation properties make those surfactants—particularly the long‐chain ones for which the DNA complexing ability was shown by means of atomic force microscopy (AFM) imaging—desirable candidates for gene‐delivery experiments.

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“…Targeting HER-2/neu overexpression has been considered an important strategy for tumor suppression [1,13,14,18,28]. Use of a recombinant monoclonal antibody against HER-2/neu increased the clinical benefit of first-line chemotherapy in metastatic breast cancer overexpressing HER-2 [21,23].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Gene Delivery to HER-2-Overexpressing Breast Cancer Cells by Modified Immunolipoplexes Conjugated with the Anti-HER-2 Antibody

et al. 2003

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Cationic liposome-mediated gene delivery to tumors has met with only limited success due to the low transfection efficiency and lack of target specificity. We developed a gene delivery system for HER-2-overexpressing cells by adding modified anti-HER-2 Fab′ fragments to liposome/DNA complexes (lipoplexes). The modified anti-HER-2-Fab′ was conjugated to liposomes containing cationic lipids such as 1,2-dioleoyl-3-(trimethylammonium) propane and cholesterol (1:1 w/w) using a maleimido-polyethyleneglycol-3400-1,2-dioleoyl-3-sn-phosphatidylethanolamine linker. The specific modification constricted the sizes of these immunolipoplexes to a range of 0.3– 0.7 µm, and they remained stable for a longer duration of time compared to the lipoplex controls (0.8–3.2 µm at 4 h). In addition, a 10-fold increase in luciferase activity was achieved after transfecting human breast cancer SK-BR3 cells with immunolipoplexes as compared to the control lipoplexes. Flow cytometry analysis demonstrated that 80% of SK-BR3 cells expressed the green fluorescent protein (GFP) 48 h after being transfected with immunolipoplexes, while only 40% of those with control lipoplexes and 3% of those with naked DNA alone expressed GFP. Furthermore, the anti-HER-2 immunolipoplexes showed specific enhancement of transfection efficiency in HER-2-overexpressing SK-BR3 cells (a 6-fold increase in luciferase activity) but not in HER-2-negative MCF-7 breast cancer cells. The enhancement of gene delivery by anti-HER-2 immunoliposomes was not affected by the presence of serum. These results demonstrate the feasibility of improving target-specific gene delivery to HER-2-overexpressing cells by insertion of lipid-modified anti-HER-2-Fab′ into the preformed liposomes.

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Current aspects of gene therapy: implications for vascular interventions

Cited by 5 publications

References 67 publications

Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides

Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides

Synthesis, Physicochemical Characterization, and Interaction with DNA of Long‐Alkyl‐Chain Gemini Pyridinium Surfactants

Enhanced Gene Delivery to HER-2-Overexpressing Breast Cancer Cells by Modified Immunolipoplexes Conjugated with the Anti-HER-2 Antibody

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