7.2.2.2 Polycation Conjugation

This method overcomes the nonspecificity of the fusion of the liposomes. This method involves the conjugation of DNA and receptor binding molecules that leads its way to the target cell.  It is then followed  by internalization by the process of endocytosis (Perales et al 1994).  One example is the use of cationic polylysine covalently linked to a ligand to cell surface receptor such as transferin, this is attached to the DNA of interest (Figure 13). The conjugate DNA complex binds to the appropriate receptor and in internalized by the receptor mediated endocytic pathway  this transporting the therapeutic gene into the cell.  The DNA moved to the nucleus where the gene is expressed.  One of the problems is the inability of the transmitted DNA to escape from the endosome. However, the presence of adenovirus help active endosomal exits especially the presence of hexon protein with other capsid proteins and such DNA escape.

The cationic conjugates are formed by the attraction of the hydrophilic domain, which is positively charged (cationic) to both the negatively charged DNA and the negatively charged cell surface. These cationic lipids were very efficient at encapsulating DNA. The main advantage of this system of gene transfer, is that the lipoplexes are non-immunogenic so they are safer than virus based methods and also its ease of preparation. But the disadvantage is low efficiency of the transfer.

Figure 13 : Gene transfer to the target cell by endocytosis of polycation conjugation