Steric Stabilization of Cationic Liposome-DNA Complexes: Influence on Morphology and Transfection Activity
Over the past few years, rapid progress has been made in controlling the in vivo delivery and expression of therapeutic genes (Blaese et al., 1995). Presently, viral-based carriers of DNA are still the most common method of gene delivery, although there is a strong research effort for developing synthetic non-viral vectors, in particular, cationic liposome-DNA complexes (CLDC) (Gao and Huang, 1995; Feigner et al., 1995; Lasic and Templeton, 1996). When compared to viral vectors, liposomal gene delivery systems offer several advantages, including the lack of viral gene elements, low immunogenic and inflammatory responses, potential for transfer of expression units of essentially unlimited size, and the possibility for cell-specific targeting (Stewart et al, 1992, Crystal, 1995.). Such preparations appeared initially to be ineffective for many in vivo applications because of instability in serum; therefore, much effort has been devoted to optimizing the complexes. This included not only synthesizing more efficient cationic lipids (Crystal, 1995; Solodin et al., 1995; Stephan et al., 1996), alternative helper lipids (Hong et al., 1997; Liu et al., 1997), as well as plasmid expression vectors (Hartikka et al., 1996), but also stabilizing the whole CLDC by polyamines and poly (ethylene glycol)-phospholipid conjugates (Hong et al., 1997). With more than 1μg protein expressed per gram of lung tissue (Hong et al., 1997; Liu et al., 1997, Templeton et al., 1997) trans-gene expression levels have recently approached those achievable with adenovirus.
KeywordsGene Delivery Mouse Serum Cationic Liposome Steric Stabilization Transfection Activity
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