**1. Introduction**

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The present chapter will be focused on different gene delivery systems used in gene therapy approaches with the purpose of inserting into individual cells and/or tissues to treat diseases. By correcting genetic defects via genome manipulation, gene therapy can truly revolutionize medical intervention for treating monogenetic inherited/acquired diseases or polygenetic conditions.

Gene therapy has undergone a remarkable development in the last 20 years. Particularly important advances have been made in the improvement of gene transfer and expression technology, with current efforts focusing on the design of safer and long-term gene expression vectors as well as systems possessing cell-type specificity for transgene delivery and regulat‐ ability of its expression by small molecules. The foreign genetic material can be administered *in vivo,ex vivo* or *in vitro* depending on the nature of a disease. A successful gene therapy system must perform several functions. In all cases, the therapeutic gene must first be delivered across the cell membrane, which is a significant barrier. Once delivered inside the cell, the therapeutic gene may exist episomally or be integrated into the host genome depending on the nature of the gene transfer vector. Moreover, an important issue is the replication and segregation of the therapeutic gene during cell division in order to maintain long-lasting gene expression. These specifications will be discussed for each gene delivery system along the chapter.


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**•** Novel systems were the viral and non-viral methods merge will be also addressed.

entangling. Tolmachov, proposes that the spontaneous entanglement of vector DNA can be enhanced by the interlacing of the DNA with sites capable of mutual transient attachment through the formation of non-B-DNA forms, such as interacting cruciform structures, intersegment triplexes, slipped-strand DNA, left-handed duplexes (Z-forms) or G-quadruplexes.

Gene Delivery Systems

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http://dx.doi.org/10.5772/56869

The liposomes, lipids arranged in lamellar structures, are concentric bilayered vesicles surrounded by a phospholipid membrane. They are related to micelles which are generally composed of a monolayer of lipids. The amphiphilic nature of liposomes, their ease of surface modification, and a good biocompatibility profile make them an appealing solution for increasing the circulating half-life of peptides, proteins, cDNAs and siRNAs (Bhavsar et al., 2012). They may contain hydrophilic compounds, which remain encapsulated in the aqueous interior, or hydrophobic compounds, which may escape encapsulation through diffusion out

**Figure 1.** Non-viral gene delivery using lipoplexes. DNA is complexed with cationic liposomes and is internalized through receptor mediated endocytosis. After their internalization large amounts of complexes are degraded in the endolysosomal compartments. Only a small fraction enters into the nucleus and elicits desired gene expression. (From:

(Tolmachov, 2012).

of the phospholipid membrane (Figure 1).

Pankajakshan Divya and Devendra K. Agrawal, 2013).

**2.2. Liposomes**
