Liposomal In vivo Gene Delivery

Hong, K., Zheng, W., Baker, A., Papahadjopoulos, D. (1997). Stabilisation of cationic liposome/DNA complexes by polyamines and polyethylenglycol-phospholipid conjugates for efficient in vivo gene delivery. FEBS Lett., 414, 187-192. 

Complexes of DNA with cationic lipid reagent, lipofectin, have been used successfully in in vivo gene delivery into cells of whole animals. Unlike the liposome delivery systems where the nucleic acids are encapsidated into liposome micelles, many micelles of cationic lipofectin form complexes with the nucleic acids. Intravenous injection of lipofectin complexes has been shown to result in the delivery of a foreign gene to lung tissue. This method has been used to introduce DNA into cells of the arterial wall in the space between the balloons of a double-balloon catheter (Nabel et al, 1990). 

Effective In Vitro and In Vivo Gene Delivery by the Combination of Liposomal Bubbles (Bubble Liposomes) and Ultrasound Exposure... 

Fig. 4. In vivo gene delivery into mouse ascites tumor cells with Bubble liposomes. S-180 cells (1x10 cells) were i.p. injected into ddY mice. After 8 days, the mice were anaesthetized, then injected with 510 p.L of pCMV-Luc (10 p.g) and Bubble liposomes (500 pg) in PBS. Ultrasound (frequency 1 MHz, duty 50% intensity 1.0 W/cm, time 1 min) was transdermally applied to the abdominal area. In another experiment, pCMV-Luc (10 pg) - Lipofectin (50 pg) or Lipofectamine 2000 (50 pg) complex was suspended in PBS (510 pL) and injected into the peritoneal cavity of mice. After 2 days, S-180 cells were recovered from the abdomens of the mice. Luciferase activity was determined, as described in Materials and Methods. Each bar represents the mean S.D. (/j=3-6). P<0.01 compared to the group treated with plasmid DNA, Bubble liposomes, ultrasound exposure or lipofection with Lipofectin or Lipofectamine 2000. LF, Lipofectin. LF2000, Lipofectamine 2000. <10 BLU/mg protein...

Kawakami S, Fumoto S, Nishikawa M (2000). In vivo gene delivery to the liver using novel galactosylated cationic liposomes. Pharm. Res. 17(3) 306-313. 

Son K K, Tkach D, Hall K J (2000). Efficient in vivo gene delivery by the negatively charged complexes of cationic liposomes and plasmid DNA. Biochim. Biophys. Acta. 1468 6-10. 

Wiseman, J.W., Goddard, C.A., McLelland, D., Colledge, W.H. (2003). A comparison of linear and branched polyethylenimine (PEI) with DCChol/DOPE liposomes for gene delivery to epithelial cells in vitro and in vivo. Gene Then, 10(19), 1654—1662. 

Several reports in the literature state that DOPE, while successfully used for in vitro gene delivery, is a poor helper lipid for in vivo applications [28-32], Instead, for reasons that are not understood, lipid mixtures for successful transfection in vivo seem to require cholesterol [33]. In fact, an equimolar mixture of cholesterol and DOTAP is widely used for in vivo experiments and clinical trials. Cholesterol has also been included in liposomes along with cationic DOTAP and fusogenic DOPE to form a potent mixture used to study the treatment of ovarian cancer by delivery of the p53 tumor suppressor gene [34, 35]. 

In vivo gene expression in animals has been obtained after introduction of DNA encapsulated in liposomes, which are lipid vesicles that entrap the DNA. Further, tissue and cell type specificity has been conferred on the liposomes by coupling to cell-type specific antibodies, resulting in immunoliposom es°. In some cases a combination of liposomes and red blood cell membranes has been used for delivery (Feigner and Rhodes, 1991). 

Dass CR, Choong PF (2006) Selective gene delivery for cancer therapy using cationic liposomes in vivo proof of applicability. J Control Release 113 155-163... 

Papahadjopoulos, D., Hong, K., Kirpotin, D., Zheng, W., Shao, V., Park, J., and Benz, C. (1997) Ligand-directed targeting of liposomes in vivo formulations for delivery of drugs and genes to tumors. Control. Rel. Bioact. Mater. 24, 159,160. 

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