Getting human gene therapy to work

Fm, Stewart

doi:10.1002/jcb.240580404

Cited by 5 publications

(3 citation statements)

References 61 publications

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“…Many of these studies employed adenoviral vectors as the vehicles for introduction of the wtp53 (Liu et al, 1994Fujiwara et al, 1994;Clayman et al, 1995;Srivastava et al, 1995;Shaw et al, 1992). The use and advantages of adenovirus for gene therapy have been recently reviewed (Bramson et al, 1995;Blau et al, 1995;Stewart, 1995). Due to its natural a nity for the epithelium of the aerodigestive tract, adenovirus is the best vehicle currently available for gene therapy studies of head and neck cancer.…”

Section: Discussionmentioning

confidence: 99%

p53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy

et al. 1997

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Section: Discussionmentioning

confidence: 99%

p53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy

et al. 1997

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“…The first gene therapy protocol to correct a genetic defect began in 1990 and was designed to treat a girl with adenosine deaminase deficiency by giving her autologous T cells that had been transduced ex vivo with a retrovirus encoding the normal gene (Blaese et al, 1995). Since that time, a variety of gene delivery techniques have been used in human trials (Crystal, 1995;Stewart, 1995).…”

Section: Introductionmentioning

confidence: 99%

Intradermal Delivery of Interleukin-12 Plasmid DNA byin vivoElectroporation

Heller

Schultz

Lucas

et al. 2001

DNA and Cell Biology

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Gene therapy depends on safe and efficient gene delivery. The skin is an attractive target for gene delivery because of its accessibility. Recently, in vivo electroporation has been shown to enhance expression after injection of plasmid DNA. In this study, we examined the use of electroporation to deliver plasmid DNA to cells of the skin in order to demonstrate that localized delivery can result in increased serum concentrations of a specific protein. Intradermal injection of a plasmid encoding luciferase resulted in low levels of expression. However, when injection was combined with electroporation, expression was significantly increased. When performing this procedure with a plasmid encoding interleukin-12, the induced serum concentrations of gamma-interferon were as much as 10 fold higher when electroporation was used. The results presented here demonstrate that electroporation can be used to augment the efficiency of direct injection of plasmid DNA to skin.

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“…Success of antisense and gene therapy depends on providing effective methods for delivery of the drugs to the site of action [1,2]. Nonviral delivery methods such as liposome-mediated DNA delivery systems offer a major advantage over the viral-based methods since lipids are less immunogenic and thus are better tolerated than virus vectors for use in in vivo systems.…”

Section: Introductionmentioning

confidence: 99%

Monitoring liposome‐mediated delivery and fate of an antisense drug in cell extracts and in single cells by capillary electrophoresis with laser‐induced fluorescence

Malek

Khaledi

2003

Electrophoresis

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Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used for evaluation of the effectiveness of delivery and fate of a model 25-mer DNA-based phosphorothiate antisense drug in cells. The antisense molecule was delivered to the cells through a simple incubation and by using a cationic liposome (Cytofectin GS 3815). The cationic lipid interacted with the negatively charged antisense to form a more positively charged complex. It was observed that uptake of the liposome-antisense complex by the cell was dependent on concentration of lipid, duration of transfection, and the cell type. The antisense drug interacted with intracellular components such as proteins and additional steps were needed to quantify the free antisense. Proteinase-K was able to release antisense from proteins. However, the addition of sodium dodecyl sulfate (SDS) to the sample or running buffer was more effective than Proteinase-K to release both naked and liposome-bound antisense from the cellular materials. Analysis of single HeLa cells for uptake of the unbound and liposome-complexed antisense revealed averages of 8.9x10(-19) moles and 4.9x10(-18) moles, respectively. The amount of uptake, however, varied greatly among individual cells and depended on the delivery method. With liposome-mediated delivery, the relative standard deviation (RSD) for the amount of antisense in individual cells was 130%, while the variation was much smaller (RSD = 45%) when the cells were incubated with the unbound antisense. These uptake variations agreed with those obtained from flow cytometry analysis.

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Getting human gene therapy to work

Cited by 5 publications

References 61 publications

p53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy

p53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy

Intradermal Delivery of Interleukin-12 Plasmid DNA byin vivoElectroporation

Monitoring liposome‐mediated delivery and fate of an antisense drug in cell extracts and in single cells by capillary electrophoresis with laser‐induced fluorescence

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