**2. Calcium phosphate**

578 Non-Viral Gene Therapy

some viral systems that integrate foreign DNA into the genome (Al-Dosari & Gao, 2009). Although viral systems such as retrovirus, adenovirus, and adeno-associated virus are potentially efficient, non-viral systems have some advantages in that they are less toxic, less

A lot of research has been conducted to find suitable non-viral systems. An ideal gene

i. It should protect the transgene against degradation by nucleases in intercellular

ii. It should be able to carry the transgene across the cell membrane and into the nucleus of

Recently, various materials have been introduced as potential gene delivery systems. Three groups of substances are more advantageous in this application. These three groups are: i. Cationic polymers (like polyethyleneimine (Kichler et al., 2001; Kircheis et al., 2001; Wightman et al., 2001), dendrimers (Tang et al., 1996; Zinselmeyer et al., 2002; Dufes et al., 2005), chitosan (Lee et al., 1998; Koping-Hoggard et al., 2001; Loretz & Bernkop-

Schnurch, 2006) and poly-L-lysine (Trubetskoy et al., 1992; Benns et al., 2000)); ii. Lipids (like liposomes (Alton et al., 1993; Templeton et al., 1997; Templeton & Lasic,

iii. Inorganic materials (like calcium phosphates (Liu et al., 2005) and silica nanoparticles

However, some limitations accompany the use of most of these systems including cell

Inorganic systems have been used in in-vitro gene delivery for many years, but their clinical application has been developed mostly in the last decade when aminofunctionalized silica was introduced. Researchers at Saarland University showed that amino-functionalized silica exhibits good gene tranfection efficiency in addition to its suitable biocompatibility (Kneuer et al., 2000; Csogor et al., 2003; Sameti et al., 2003). Because of this, several studies have been conducted on using amino-funtionalized silica as a gene delivery system (Bharali et al., 2005; Roy et al., 2005; Klejbor et al., 2007; Choi et al., 2008). Research was also conducted on using silica in combination with other polymers for gene delivery. Results demonstrated that making composites of certain polymers with silica nanoparticles could enhance transfection efficiency due to the dense

There is an increasing interest in mesoporous silica for drug/gene delivery applications because of their higher capacity and of the potential for tailored release of the active molecule. Some studies have been conducted on functionalized or non-functionalized mesoporous silica but the research on using this type of inorganic systems is still ongoing

Some studies have been done on using functionalized gold nanoparticles as a gene delivery system. The results demonstrated the feasibility of using this approach, but further research

In addition to calcium phosphate, (their gene delivery application is reviewed in this chapter), other inorganic systems have also been studied regarding in-vitro gene delivery to

immunogenic, and easier to prepare (Nishikawa & Huang, 2001).

iii. It should have no detrimental effects (Gao et al., 2007).

(Kneuer et al., 2000; Csogor et al., 2003; Sameti et al., 2003)).

toxicity, immune response and low tranfection efficiency.

nature of silica nanoparticles (Luo et al., 2004).

is needed in this new area (Liang et al., 2010; Niidome et al., 2011).

(Park et al., 2008; Slowing et al., 2008).

delivery method needs to meet 3 major criteria:

matrices.

1999));

**1.2 Inorganic vectors** 

targeted cells.

The work of Graham and Van Der Eb completed in 1973 shows the first application of calcium phosphate in condensation of genetic materials. The brilliant results of their research were that calcium phosphate could condense DNA and increase the transfection efficiency with a relatively simple procedure (Graham & Van Der EB, 1973a). This first research led to vast application of this technology in in-vitro gene delivery because of the demonstrated easy preparation method and proper results.

In order to have a better understanding of calcium phosphate gene delivery properties, first we shall have a look at the structure and characteristics of the calcium phosphate family.
