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Development of more efficient and safer gene carriers using nonviral compounds is one of the most challenging aspects of gene therapy (Kay, 1997; Lasic, 1997). Compared to viral carrier systems, nonviral gene carrier systems have advantages in simplicity of use, lack of specific immune response, and ease of mass production due to the low cost of preparation; however, they have the disadvantage of low transfection efficiency, which needs to be overcome (Miller, 1998; Li & Huang, 2000). To improve the efficiency of nonviral carriers, many synthetic organic compounds, including cationic lipids (Felgner & Ringold, 1989; MacDonald et al., 1999; Felgner et al., 1987; Behr et al., 1989; Meyer et al., 1998), polycations (Boussif et al., 1995; Petersen et al., 2002; Koide et al., 2006; Russ et al., 2008; Haensler & Szoka, 1993; Shim & Kwon, 2009), and combinations thereof (Guillot-Nieckowski et al., 2007; Wu et al., 2001; Ewert et al., 2006; Takahashi et al., 2007; Matsui et al., 2006; Mustapa et al., 2009; Kogure et al., 2008), have been developed as nonviral gene carriers (Mintzer, M. A. & Simanek, E. E., 2009; also references cited therein). Substantial research has been reported on structure–activity relationships for cationic amphiphiles concerning the cationic and hydrophobic portions (Remy et al., 1994; Geall et al., 1999; Ewert et al, 2002; Byk et al., 1998; McGregor et al., 2001). Such amphiphiles form self-assembling micelles and liposomes in an aqueous phase, the structures of which have been investigated using small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) to gain knowledge about structure–activity relationship, particularly those involving ordered structures (lamellar, inverted hexagonal, and cubic phases) and their morphological changes (Koltover et al., 1998; Koynova, Wang & MacDonald, 2006) as well as about the size of complexes (Aoyama et al., 2003). The mechanism of gene delivery by such cationic carriers probably involves an endosomal pathway (Wrobel & Collins (1995)): (i) cellular uptake via endocytosis, (ii) DNA release from endosome, and (iii) entry into the nucleus. Many researchers have devised cationic compounds that facilitate the process, for example, ligand-conjugated molecules targeting a receptor such as integrin (Mustapa et al., 2007; Varga, Wickham & Lauffenburger, 2000), pH-responsive or cleavable molecules that enable escape of DNA from endosome (Russ et al, 2008; Oupicky, Parker & Seymour, 2002; Dauty et al., 2001; Miyake et al., 2004; Anderson,

Polyamine – Lipid Conjugates as Effective Gene Carriers: Chemical Structure, Morphology, and Gene Transfer Activity