Liposomes in gene delivery

DD Lasic. Liposomes in Gene Delivery. Boca Raton, FL CRC Press, 1997. 

The major obstacle for the use of this type of liposomes in gene delivery was their intrinsically poor encapsulation efficiency of ultra-large payload compounds... 

Duncan JE, Whitsett JA, Horowitz AD (1997) Pulmonary surfactant inhibits cationic liposome-mediated gene delivery to respiratory epithelial cells in vitro. Hum Gene Ther 8(4) 431-438... 

Liu Y, Fong S, Debs RJ. Cationic liposome-mediated gene delivery in vivo. Methods Enzymol 2003 373 536-550. 

Nicolau, C., Papahadjopulos, D. (1998). Gene therapy liposomes and gene delivery— a perspective. In Lasic, D. and Papahadjopoulos, D., eds., Medical Applications of Liposomes. Elsevier, Amsterdam, 347-352. 

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. 

Lipid moieties coupled to polyethylene glycol (PEG) have been used to increase the blood circulation time of lipoplexes (Fig. 32). The PEG-lipid conjugates such as DOPE-PEG, Chol-PEG, ceramides-PEG and their derivatives are then coformulated with the cationic lipid, helper lipid, and DNA. This results in coating the surface of the lipoplexes with PEG and preventing undesired association with plasma proteins or circulating cells (stealth liposomes). Recently, a-tocopheryl PEG-succinate (TPGS) was also used in gene delivery formulations because of its ability to confer not only a stealth property but also antioxidant and absorption enhancer properties [129]. 

Liposome-mediated gene delivery is dependent on numerous factors, such as, the formulation of the liposomes including the cationic lipid/neutral lipid ratio, how the liposomes are prepared, the cationic liposome/DNA charge ratio of the complex of cationic liposome and DNA (lipoplex), and the method used to produce the lipoplex. Recently, it was reported that the way in which a liposome was prepared affected transfection efficiency (1), and formation method of lipoplex affected size of lipoplex in which large ones increased the efficiency of transfection (2-7). 

Shape. Lin et al. demonstrated a correlation between lipoplex structure and transfection efficiency [102]. Liposomes that formed hexagonal structures were more efficient in gene delivery than those that formed a lamellar, owing to improved fusion with mouse cell membranes (both endosomal and plasma membranes), whereas lamellar structures remained stable inside the cell. This correlation of structure and transfection efficiency was used to explain the increased efficiency of DOTAP DOPE liposomes (hexagonal structures) compared to DOTAP DOPC liposomes (lamellar structures) [102],... 

Alton NFW, Middleton PG, Caplen NJ, Smith SN, Steel DM, Munkonge FM, Jeffery PK, Geddes DM, Hart SL, Williamson R, Fasold KI, Miller AD, Dickinson P, Stevenson BJ, Molachlan G, Dorin JR, Porteous DJ. Noninvasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice. Nat Genet 1993, 5, 135-142. 

M. Preuss, M. Tecle, 1. Shah, D. A. Matthews and A. D. MiUer, Comparison between the interactions of adenovirus-derived peptides with plasmid DNA and their role in gene delivery mediated by liposome-peptide-DNA virus-like nanoparticles, Org. Biomol. Chem., 2003,1, 2430-2438. 

Godbey, D.A.B.A. Liposomes for Use in Gene Delivery. Journal of Drug Delivery... 

Liposomes and lipoplexes are usually self-assembling, easy to prepare and biodegradable. They allow increased uptake of naked DNA and DNA NPs. They can also be combined with polycations to form lipid-DNA NPs. Caracciola et al. [8] observed that lipid-protamine-DNA (LPD) NPs were more efficient than lipoplexes for gene delivery in CHO (Chinese hamster ovary cells), HEK293 (human embryonic kidney cells), NIH 3T3 (mouse embryraial cells) and A17 (murine cancer cells) cells. Unfortunately, cationic liposomes exhibit significant variability in gene delivery efficiency and are often toxic to cells. 

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