21 - Use of Antisense Oligodeoxynucleotides to Block Gene Expression in Central Nervous System

Abstract

This chapter provides an overview of the use of antisense oligodeoxynucleotides to block gene expression in central nervous system. Antisense oligodeoxynucleotides that gain access to the cellular cytoplasm are believed to block translation by one of two mechanisms. The antisense oligonucleotides may hybridize to the mRNA and as a result of steric hindrance, or so-called hybridization arrest, prevent the formation of the ribosomal complex and hence translation. Alternatively, the antisense oligonucleotides may hybridize to any region of the mRNA and form a substrate for the nucleases RNase H. Antisense DNA is the most commonly used form of antisense both because of its convenience and relatively low price. The parameters to be considered in constructing an antisense oligonucleotide for use in the central nervous system are usually similar to those for any other system. When RNase H activity is a contributing factor to antisense action, the oligonucleotide can be made complementary to any portion of the mRNA and be effective. One of the major challenges in the use of antisense oligonucleotides in vivo is to deliver the agent to the target organ with sufficient duration and concentration to block gene expression effectively.