Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA

Liu, F; Song, Young K.; Liu, D

doi:10.1038/sj.gt.3300947

Cited by 1,602 publications

(1,664 citation statements)

References 25 publications

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“…(i) The simplest, of course, is the injection of naked DNA, which in the skeletal or cardiac muscle leads to some expression of the injected genes; [1][2][3] however, this expression is very low and very variable from sample to sample. (ii) The hydrodynamic method consists in the very rapid injection through the mouse tail vein of a large volumes of DNA solution: it results in a very efficient transfection of liver cells, even though the procedure is somehow dangerous for the treated mice; [4][5][6] indeed, part of the mechanism is based on the transient heart failure resulting from the injection, which blocks the fluid distribution in the body and provokes a liquid overpressure in the liver. 6 (iii) For physical DNA transfer to superficial tissues like the skin or the leaves in the plant kingdom, the 'biolistic' approach ('jet injection' and 'gene gun') also leads to good transfection levels.…”

Section: Introductionmentioning

confidence: 99%

DNA electrotransfer: its principles and an updated review of its therapeutic applications

2004

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Section: Introductionmentioning

confidence: 99%

DNA electrotransfer: its principles and an updated review of its therapeutic applications

2004

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“…13 Successful transfer and expression in the liver can also be achieved by systemic administration of naked plasmid using a hydrodynamic-based procedure. 14,15 One major concern for this technique is that it requires an injection volume of 8% of the body weight, which may alter the physiological conditions of the liver. Localized hepatic gene expression has also been achieved using direct hepatic DNA injection.…”

Section: Introductionmentioning

confidence: 99%

Increased receptor-mediated gene delivery to the liver by protamine-enhanced-asialofetuin-lipoplexes

2003

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A novel lipidic vector composed of DOTAP/Chol liposomes, asialofetuin (AF), protamine sulfate and DNA has been developed. The resulting protamine-AF-lipoplexes improved significantly the levels of gene expression in cultured cells and in the liver upon i.v. administration. Lipoplexes containing the optimal amount of AF (1 mg/mg DNA) showed a 16-fold higher transfection activity in HepG2 cells than nontargeted (plain) complexes. The uptake by cells having asialoglycoprotein receptors (ASGPr) on their plasma membrane was decreased by the addition of free AF, indicating that AF-lipoplexes were taken up specifically by cells via ASGPr-mediated endocytosis. Results from transfections performed in cells defective in ASGPr, ie HeLa cells, confirmed this mechanism. By addition of the condensing peptide, protamine sulfate, smaller complexes were obtained, which enhanced even more the uptake of AFcomplexes in HepG2 cells and in the liver. The optimal amount of protamine was 0.4 mg/mg DNA, and gene expression was about 5-fold over that obtained with AF-lipoplexes in the absence of the peptide, and 75-fold higher than that with plain conventional lipoplexes. Protamine-AF-lipoplexes increased by a factor of 12 luciferase gene expression in the liver of mice administered systemically via the tail vein, compared to plain complexes. In summary, our findings extend the scope of previous studies where AF-lipoplexes were used to introduce DNA into hepatocytes. The combination of targeting and protamine condensation obviated the need for partial hepatectomy, commonly required to obtain efficient gene delivery in this organ. Since protamine sulfate has been proven to be non-toxic in humans, the novel liverspecific vector described here may be useful for the delivery of clinically important genes to this organ.

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“…[10][11][12] As a result, the animals were highly resistant to a subsequent lethal HSV-1 challenge. 13 The surviving mice also escaped latent infection, which was not reported in earlier studies using intramuscular pDNA vaccination.…”

Section: Introductionmentioning

confidence: 99%

Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice

Asada

Mei

et al. 2004

Gene Ther

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Intravascular plasmid DNA (pDNA) vaccine encoding herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) effectively induces prophylactic immunity against lethal HSV-1 infection in mice. We investigated whether the vaccine potency is further improved by coadministration of cytokine genes together with a low dose of genetic vaccine. pDNA encoding IL-12, IL-15, IL-18 or IL-21 was capable of elevating survival rates of HSV-1-infected mice when coinjected with 1 mg of gB pDNA, while IL-10 gene delivery failed to affect the effectiveness of the genetic immunization. Although only 17% of mice survived acute HSV infection after the gB pDNA vaccination at a dose of 1 mg, all mice coadministered with 1 mg each of gB and IL-12 pDNAs not only survived the acute infection but also escaped latent infection. In these animals, the neutralizing antibody against HSV-1 was abundantly produced, and CTL activity against the gB antigen was augmented. Coadministration of the gB and IL-12 genes also elevated the serum level of interferon-g. Adaptive transfer experiments indicated that soluble factors contributed to preventive immunity, while cell components alone were not capable of protecting mice from fatal viral infection. These results strongly suggest potential usefulness of Th1 cytokine genes as effective molecular adjuvants that facilitate specific humoral as well as cellular immune responses elicited by intravascular molecular vaccination.

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Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA

Cited by 1,602 publications

References 25 publications

DNA electrotransfer: its principles and an updated review of its therapeutic applications

DNA electrotransfer: its principles and an updated review of its therapeutic applications

Increased receptor-mediated gene delivery to the liver by protamine-enhanced-asialofetuin-lipoplexes

Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice

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