Applications of antisense oligodeoxynucleotides in immunology and autoimmunity research

Abstract

Antisense oligodeoxynucleotides (oligos or oligonucleotides) can be useful agents for studying the role of immunologically relevant genes. Dozens of laboratories have reported antisense inhibition of a wide variety of cytokines, growth factors, proto-oncogenes, and other targets of interest to immunologists. In addition to the potential applications for antisense oligos as research tools in immunologic studies, there is increasing interest in their possible therapeutic applications. Advances in the molecular biology of immunity and autoimmunity are leading to the identification of genes whose abnormal expression could contribute to disease pathogenesis. Antisense technology may provide therapies precisely targeted to the molecular genetic inducers of human disease. Despite this bright promise, some genes or experimental systems may not be amenable to the antisense approach. Potential explanations for failed antisense experiments include such factors as nonsequence-specific effects, oligonucleotide degradation, insufficient oligonucleotide uptake, inaccessibility of the RNA target region to the oligonucleotide, and a long half-life of the target protein. This article focuses on the practical factors that may be important in optimizing antisense efficacy.