ABSTRACT
Gene therapy is a promising approach for treatment or prevention of wide range of diseases associated with defective gene expression. It involves the insertion of a therapeutic gene into cells, followed by expression and production of the required proteins. Two main delivery systems, including viral or non-viral gene carriers, are currently deployed for gene therapy. Although viruses are currently the most commonly researched vector, however, the need to resolve drawbacks related to viral vectors (e.g., high risk of mutagenicity, immunogenicity, low production yield, limited gene size) led to the development of non-viral vectors. Several non-viral modalities are reported to transfer foreign genetic material into cells; cationic polymers constitute one of the most promising approach. For this reason, various cationic polymers with diminished cytotoxicity and enhanced efficacy are rapidly emerging as systems of choice. This chapter provides an overview and recent developments of cationic polymers employed for in vitro
and in vivo delivery of therapeutically important nucleotides, e.g., DNA and siRNA. The mechanism and recent progress in cationic polymer based gene delivery are reviewed in detail. 2.1 IntroductionThe basic concept of gene therapy is that disease can be treated by transfer of genetic material into specific cells of a patient to supplement defective genes responsible for disease development. Stribley et al. demonstrated two strategies involved for the application of gene delivery: (i) Corrective therapy — correction of genetic defects in target cells — is exploited for the treatment of diseases with single gene disorders like severe combined immunodeficiency syndromes, cystic fibrosis, hemophilia, sickle cell anemia, β-thalassemia, muscular dystrophy and lignant tumors, including ovarian carcinoma, and (ii) cytotoxic gene therapy — destruction of target cells using a cytotoxic pathway; it is used for the treatment of malignant tumors, including ovarian, breast, and endometrial carcinomas.1 The fundamental idea is to deliver the gene to cells or tissues. It may be activation, silencing, introducing or gene knock out and knock down both in vitro and in vivo toward cells, and the possibilities for interventions.2 Successful gene therapies depend on the efficient delivery of genetic materials into the cell nucleus and its effective expression within these cells. DNA can be delivered into the cell nucleus either using physical means or by specific carriers that carry the genes into the cells. Number of techniques has been developed for DNA delivery, including direct introduction of transgene using cell electroporation, microinjection of DNA, and incorporation of the gene by vectors.3 Vectors for delivering genes can be divided into two main groups: (a) Viral carriers, where the DNA to be delivered is inserted into a virus, and (b) cationic molecular carriers, which forms electrostatic interactions with DNA for delivering gene to cells and includes polymers and lipids.4 Viral vectors, including retroviruses, adenoviruses, and adeno-associated viruses, are effectively used for introducing genetic material into host cells,5 but immunogenicity, inflammatory effects, and safety concerns with use of these viruses restrict their usefulness.
