Gene delivery cationic liposomes

Formation of a complex between DNA and polycationic compounds appears to be the initial and quite possibly a critical parameter for nonviral gene delivery. Several synthetic vector systems, which are generally cationic in nature, including poly(lysines), cationic liposomes or various types of block copolymers and recently dendrimers, have been shown to self-assemble with plasmid DNA [13-15] [16]. Specific physicochemical properties manifested by these DNA complexes depend on the type of cationic agent used however, interesting patterns for such interactions are beginning to evolve [17, 18]. Under certain conditions, the interaction of DNA with polyvalent cations results in... 

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... 

Audouy SA, de Leij LF, Hoekstra D, Molema G. In vivo characteristics of cationic liposomes as delivery vectors for gene therapy. Pharm Res 2002 19(11) 1599-1605. 

Meyer O, et al. Cationic liposomes coated with polyethylene glycol as carriers for oligonucleotides. J Biol Chem 1998 273 15621 Shi G, et al. Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations. J Control Release 2002 80 309. 

One of the principal forms of nonviral delivery is liposome-mediated gene transfer, in which the DNA is enveloped in a cationic lipid that acts as a shield against the degradation or inactivation of the DNA during the process of gene transfer. 

Duzgunes N, De Ilarduya CT, Simoes S, et al. Cationic liposomes for gene delivery novel cationic lipids and enhancement by proteins and peptides. Curr Med Chem 2003 10 1213-1220. 

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

Gao X, Huang L. Potentiation of cationic liposome-mediated gene delivery. Biochemistry 1996 35(3) 1027-1036. 

Simoes S, Slepushkin V, Gaspar R, et al. Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides. J Biol Chem 1998 5(7) 955-964. 

Birchall, J. C., et al.. Gene expression in an intact ex-vivo skin tissue model following percutaneous delivery of cationic liposome-plasmid DNA complexes. Int. J. Pharm., 197, 233-38, 2000. 

Several vectors have been used in an attempt to deliver the cf gene to the airway epithelial cells of sufferers. The most notable systems include adenoviruses and cationic liposomes. Vector delivery to the target cells can be achieved directly by aerosol technology. Delivery of cftr cDNA to airway epithelial cells (and subsequent gene expression) has been demonstrated with the use of both vector types. However, in order to be of therapeutic benefit, it is essential that 5-10% of the target cell population receive and express the cftr gene. This level of integration has not been... 

The therapeutic efficacy of either systemic or local pulmonary delivery of the IFN-y gene was evaluated in a murine allergen-induced airway hyperresponsiveness (AHR) model (Dow et al. 1999) and it was found that a high efficiency of gene transfer could be achieved. Intratracheal administered cationic liposomes were prepared from a mixture of l,2-diacylglycero-3-ethylphosphocholine (EDMPC) and cholesterol. Intravenous injections were prepared from l,2-dioleyl-3-trimethylammo-ninm propane (DOTAP) and cholesterol and compared with pulmonary administered... 

Liu, Y., Mounkes, L.C., Liggitt, H.D., et al. (1997). Factors influencing the efficiency of cationic liposome-mediated intravenous gene delivery. Nat. Biotechnol., 15, 167-173. 

Nonviral vector systems are usually either composed of a plasmid based expression cassette alone ( naked DNA), or are prepared with a synthetic amphipathic DNA-complexing agent (84, 88). Gene delivery systems based on nonviral vectors mainly comprise cationic liposomes, DNA-polymer-protein complexes, and mechanic administration of naked DNA. An idealized/optimized multifunctional nonviral gene delivery system is depicted in Figure 13.4. 

Successful gene delivery by use of cationic liposomes requires the following conditions (134) (1) condensation of DNA into the complex and its protection from degradation by intracellular nucleases (2) adhesion of DNA-lipid complex onto the cellular surface (3) complex internalization (4) fusion of an internalized DNA-cationic liposome complex with the endosome membrane (5) escape of DNA from the endosome (6) entry of DNA into the nucleus followed by gene expression. 

Cullis, P.R., Chonn, A. (1998). Recent advances in liposome technologies and their applications for systemic gene delivery. Adv. Drug Deliv. Rev., 30(1-3), 73-83. Audouy, S.A., de LeiJ, L.F., Hoekstra, D., Molema, G. (2002). In vivo characteristics of cationic liposomes as delivery vectors for gene therapy. Pharm. Res., 19(11), 1599-1605. 

Pedroso de Lima, M.C., Neves, S., Filipe, A., Duzgunes, N., Simoes, S. (2003). Cationic liposomes for gene delivery from biophysics to biological applications. Curr. Med. Chem., 10(14), 1221-1231. 

Almofti, M.R., Harashima, H., Shinohara, Y., Almofti, A., Baba, Y., Kiwada, H. (2003). Cationic liposome-mediated gene delivery Biophysical study and mechanism of internalization. Arch. Biochem. Biophys., 410(2), 246-253. 

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. 

Zuidam, N.J., Barenholz, Y. (1997). Electrostatic parameters of cationic liposomes commonly used for gene delivery as determined by 4-heptadecyl-7-hydroxycoumarin. Biochim. Biophys. Acta, 1329, 211-222. 

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