Gene delivery cell fusion

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],... 

Figure 7.1-3. The ideal synthetic (nonviral) gene delivery vector. After dense DNA packaging is accomplished (e.g., by protamine sulfate), the surface of synthetic particles (which is usually positively charged) needs to be shielded (e.g., by poly (ethylene-glycol) [PEG]) so that they do not attach to blood elements or to each other and, therefore, have an extended circulating plasma half-life (1) (passive targeting to leaky vessels ). The surface of the particles will contain specific ligands for active targeting to selected cells/ tissues (2). By engineering viral fusion proteins to the particle coat, cell entry is facilitated...

Liposomes Liposome-based gene transfer is anonviral gene delivery method that uses the combination of phospholipids, cholesterol, and some polymers for the formation of spherical vesicles. DNA is dehvered into cells by liposomes via membrane fusion and endocytosis. This method has several advantages such as enhanced delivery, nontoxicity, the protection of nucleic acids from nuclease activity, and the abihty to target DNA into a variety of ceU types, including protoplasts, via plasmodesmata. 

Several enveloped viruses, and some physical gene transfer techniques such as electroporation, deliver the nucleic acid into the cell by direct crossing of the cell membrane. Lipid-based, enveloped systems can do this by a physiological, selfsealing membrane fusion process, avoiding physical damage of the cell membrane. For cationic lipid-mediated delivery of siRNA, most material is taken up by endo-cytotic processes. Recently, direct transfer into the cytosol has been demonstrated to be the bioactive delivery principle for certain siRNA lipid formulations [151]. 

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