Cell-based gene delivery

Uherek, C., Fominaya, J. and Weis, W. (1998) A modular DNA carrier protein based on the structure of diphteria toxin mediates target cell-specific gene delivery. J. Biol Chem., 273, 8835-8841. 

DNA binding moiety has been synthesized and evaluated as a receptor-mediated gene delivery system. The system was able to transfect about 30% of corneal endothelial cells of rabbit, pig and human in the presence of chloroquine (Shewring et al., 1997). Associated with the fusogenic peptide of influenza, this peptide transfected 25-30% of primary cultures of vascular smooth muscle cells of man, rabbit and rat (Collins et al., 2000 Li et al., 2000). The molossin-based gene delivery system represents an interesting system in transplantation because the molossin peptide does not bind to vascular endothelium and pancreatic islets. 

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. 

Nah, J.W., L. Yu, S.O. Han, C.H. Ahn, and S.W. Kim. 2002. Artery wall binding pep-tide-poly(ethylene glycol)-grafted-poly-(L-lysine)-based gene delivery to artery wall cells. /. Control. Release 78 273-284. 

The initial viral-based gene delivery experiments were performed in vitro using replication defective retroviral vectors in an attempt to transduce endothelial cells (Yao et al., 1991). Preliminary viral-based in vivo cardiovascular gene delivery experiments were also performed using retroviral vectors and demonstrated this vector system s ability to successfully transduce vascular endothelial cells (Newman et al., 1991). Although attempts at direct transduction of the carotid artery were not successful, it was established that efficient endothelial transduction could be achieved through the retrovirus-mediated infection of cells ex vivo and their subsequent arterial seeding in vivo (Lynch et al., 1992). 

Cioffi L, Sturtz FG, Wittmer S, et al. A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E. Gene Ther 1999 6(6) I 153-1 159. 

DNA delivery has been a significant challenge over the last decade. Therapeutic efficacy with significant endonu-clear delivery has restricted the DNA-based therapeutic applications. Previously, Dekie et al. showed the development of PGA-based gene delivery vectors [271]. The complexes formed between the DNA and the PGA were shown to be extremely stable and were shown to successfully transfect target cells. 

Despite the advances in polymer-based gene delivery systems in order to achieve an optimal balance between the conflicting requirements for DNA protection during the transport and the efficient release into the cells, more complex delivery vehicles have been developed. 

NP-Based Gene Delivery for Stem Cell Isolation and Culture... 

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