Chapter 11 - Viral and Nonviral Vectors for In Vivo and Ex Vivo Gene Therapies

Abstract

Gene therapy is the therapeutic delivery of nucleic acids for treatment of genetic diseases into patient’s cells. They might be either expressed as proteins, interfere with the expression of proteins, or possibly even correct genetic mutations. But this may be approached by two different ways: (1) ex vivo, which is when cells are modified outside the body and then transplanted back again. Cells from the patient’s blood or bone marrow are removed and grown in the laboratory to be genetically modified by different molecular biology techniques on a dish. This also involves the so-called cell therapy which is now widely used. (2) But also gene therapy could be approached by in vivo therapy, in which the gene is transferred into the cells inside the patient's body. However, an efficient transfer of the genetic material into a cell is necessary to achieve the desired therapeutic effect. The therapeutic molecule is packaged into vehicles called vectors, but the “vector” is used to carry the nucleic acid inside the cells within the body, facilitating the transfer of genetic information into a cell. The simplest way to perform gene therapy involves the use of therapeutic naked DNA that encodes a functional gene to replace a mutated version of the defective gene. In most cases, a relatively large piece of genetic material (>1kb) is required which includes the promoter sequences that activate the expression of the gene, the coding sequences that direct the production of a specific protein, and signaling sequences that direct RNA processing such as polyadenylation. In this way, no vector would be required but the efficiency of this methodology was demonstrated to be low. Vectors can be divided into viral and nonviral delivery systems. The two major methods are those that use biological nanoparticles (mainly recombinant viruses or also called viral vectors, although recently exosomes are taking a place among the biological vectors for genetic transfer) and those that use chemical nanoparticles on DNA complexes or naked DNA (nonviral methods). In this chapter, we will review both categories and their applications in clinical trials.