Modulation of gene expression by antisense oligonucleotides
INTRODUCTION One of the major developments in modern biomedical research is genetic therapy, which is based on progress made in molecular biology and genetics, especially the identification, cloning, sequencing and characterization of pathogenic genes. Major efforts in the development of genetic therapy can be summarized in two general approaches. The first is the introduction of a vector that is capable of inserting into the genetic code a gene of interest that may restore a normal function or correct an abnormal function. This approach is termed gene therapy. The second, termed antisense therapy, delivers to the target cells antisense molecules that target RNA or DNA with which they hybridize and specifically inhibit the expression of pathogenic genes. In the past, the term antisense has been used to include four distinct approaches, including classical antisense or anticode, ribozyme or catalytic RNA, triplex or antigene, and aptamer technologies. These antisense technologies are compared in Table 3.1.