Gene delivery mechanisms

Another novel cardiovascular therapy that has recently come into play is the use of stem cell delivery. These approaches have thus far involved the use of gene delivery mechanisms to essentially force embryonic stem cells into cardiomyocyte differentiation with the goal of producing a cardiac pace-making cell (Arruda et al., 2004). Researchers are also developing methods for utilizing seeded adult mesenchymal stem cells as an implanted base to act as a depot for the delivery of localized gene therapies (Arruda et al., 2004). 

In this chapter, we describe the synthetic strategy for bio-inorganic conjugates which can be used as drug or gene delivery systems and their efficient cellular uptake mechanism. 

CNTs with different characteristics, which will lead to differences in the mechanism of CNT metabolism, degradation or dissolution, clearance and bioaccumulation. On the other hand, most non-viral gene delivery systems today suffer from both limited levels of gene expression and an unfavourable toxicity profile due to their highly cationic surface character. Therefore, opportunities for CNT-based gene transfer systems are still ample. 

Feigner JH, Kumar R, Sridhar CN, et al. Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations. J Biol Chem 1994 269(4) 2550-2561. 

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. 

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. 

Barron, L.G. and Szoka, F.C. (1999) The perplexing delivery mechanism of lipoplexes. In L.Huang, M.-C.Huang and E. Wagner (eds) Nonviral Vectors for Gene Therapy. Academic Press, pp. 224-264. 

Anti-deoxyribonucleic acid autoantibodies from human and mice suffering from Lupus erythematosus can penetrate into cells and accumulate in the cell nucleus. Based on the characteristics of a mi-ON A autoantibodies, VAYISRGGVSTYYSDTVKGRFTRQKYNKRA peptide (P3), which exhibits a-helix, has been used as a vector for the intracytoplasmic and intranuclear translocation of macromolecules (Table 16.7) (Avrameas et al., 1998, 1999). P3 shares similar capabilities with Antenapedia peptide (Derossi et al., 1994), but in contrast P3 operates only at 37 °C by an energy dependent mechanism. P3 linked to a 19 lysine residue sequence (K19-P3) forms complexes with plasmid DNA. Efficient transfection of mouse 3T3 cells and hamster lung CCL39 cells were obtained with these complexes. This transfection was not impaired by the presence of serum and did not require helper molecules such as chloroquine. These observations suggest that peptides from cell specific anti-DNA autoantibodies may represent a source of peptide-based gene delivery system with different specificities. 

Three families of polymers have been used to study transfection mechanisms polyamines, polyamides, and polyvinyl type polymers. The transfection efficiencies achievable with these systems vary widely, so an in-depth analysis of each polymer family and subsequent comparison of what affects gene delivery will be discussed in this chapter. In addition to high transfection efficiency, it is important for the polymeric systems to be relatively nontoxic to cells in vitro and not to elicit an immune response in vivo. Thus, the effect of transfection parameters on cytotoxicity and immunogenicity will also be examined. 

Venugopalan P, Jain S, Sankar S, Singh P, Rawat A, Vyas SP (2002) pH-sensitive liposomes mechanism of triggered release to drug and gene delivery prospects. Pharmazie 57( 10) 659-671... 

Cationic Liposome-Nucleic Acid Complexes for Gene Delivery and Silencing Pathways and Mechanisms for Plasmid DNA and siRNA... 

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