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**23** 

*Iran* 

**Toxicogenomics of Nonviral Cationic** 

*Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz* 

To date, both viral and nonviral vectors have been exploited for delivery of gene-based therapies to target cells/tissues. Despite high efficiency of the viral vectors (e.g., retroviruses and adenoviruses), these vectors appear to be immunogenic and potentially harmful when used in clinical gene therapy protocols (Ferber, 2001b). Besides, the preparation and purification of the viral vectors appear to be laborious, cost-prohibitive and not amenable to industrial-scale manufacture. Nonviral vectors such as cationic lipids (CLs) and cationic polymers (CPs) have been categorized as advanced materials and their low immunogenicity, lack of pathogenicity, and ease of pharmacologic production continue to make them attractive alternatives to viral vectors (Medina-Kauwe et al., 2005). However, these vectors may also suffer from relatively low levels of gene transfer compared to viruses. Thus, the drive to advance these vectors continues resulting in considerable progresses in improved transfection efficiency. Nonviral vectors (in particular cationic gene delivery systems) are able to bind and enter the target cells, however they yield low gene expression. No substantial information is available on interactions of these vectors with cellular biomolecules. Since these medicaments tend to act at genomic levels, thus understanding the genomic impacts of the nonviral vectors may help develop more efficient gene delivery systems. Nonetheless, this needs

To date, exploitation of the "omics" concepts (e.g., genomics, proteomics and metabolomics) is going to change the face of pharmacotherapy towards significantly more advanced and efficient pharmaceuticals (e.g., gene based nanomedicines) with minimal adverse consequences (Aardema & MacGregor, 2002). Enormous efforts have also been devoted for application of the global gene expression profiling in pharmacologic and toxicological investigations. The gene expression profiling technology has been primarily exploited for identification of underlying mechanisms for toxicity of pharmaceuticals and their genomic signatures, by which the safety liabilities can be determined and manifestations of undesired genotoxicity can be prohibited (Suter et al.,

This methodology can be successfully used for the discovery and development of any chemicals and pharmaceuticals including gene delivery nanosystems. The main focus of the current book chapter is to provide some useful information about "genocompatibility" and

recruitment of high throughput screening methodologies.

**1. Introduction** 

2004; Yang et al., 2004).

**Gene Delivery Nanosystems** 

Yadollah Omidi, Vala Kafil and Jaleh Barar *Research Center for Pharmaceutical Nanotechnology* 

