Non-Viral Delivery Systems in Gene Therapy and Vaccine Development

Abstract

Gene therapy is the process of treating a particular disease through the introduction of genetic material in order to elicit a therapeutic benefit [Stone, 2010]. The defective gene of a diagnosed patient can be corrected by a number of different strategies such as “gene replacement”, “gene correction”, and “gene augmentation” [Katare and Aeri, 2010]. In replacement therapy, a normal gene is inserted somewhere in the genome so that its product could replace that of a defective gene. This approach may be suitable for recessive disorders, which are marked by deficiency of an enzyme or other proteins. Although, the gene functions in the genome providing an appropriate regulatory sequence, the approach may not be successful in treating dominant disorders associated with the production of an abnormal gene product, which interferes with the product of normal gene [Katare and Aeri, 2010]. Corrective gene therapy requires replacement of a mutant gene or a part of it with a normal sequence. This can be achieved by using recombinant technology. Another form of corrective therapy involves the suppression of a particular mutation by a transfer RNA that is introduced into a cell [Katare and Aeri, 2010]. In gene augmentation, introducing a normal genetic sequence into a host genome modifies the expression of mutant gene in defective cell and the defective host gene remains unaltered. In general, the gene therapy recipient cells may be germline cells or somatic cells. Germline cells therapy involves modifying the genes in germ cells which will pass these genetic changes to the future generations. Somatic cells therapy involves the insertion of genes into specific somatic cells like the bone marrow stem cells, fibroblasts, hepatocytes or mycocytes [Katare and Aeri, 2010]. This form of gene therapy is being used at most genetic engineering laboratories throughout the world. Clearly, gene therapy provides great opportunities for treating diseases from genetic disorders, infections and cancer [Park et al., 2006]. While the genetic mutations underlying various diseases are well understood, delivering a corrective gene to the unhealthy organs/tissues remains a remarkable challenge [Stone, 2010]. To achieve successful gene therapy, development of proper gene delivery systems could be one of the most important factors. Gene delivery systems should be designed to protect the genetic materials from premature degradation in systemic blood stream and to efficiently transfer the therapeutic genes to target cells. Intracellular delivery systems will be required for all molecules that have intracellular function. For example, nucleic acid molecules including encoding genes, oligonucleotides and RNA molecules must enter cells and target the nucleus when transcription is the target. Regardless of the molecules for delivery, a common requirement