**1. Introduction**

Over the past decade, it is known that the advent of oligonucleotide-based gene inactivation agents have provided potential for these to serve as analytical tools and potential treatments in a range of diseases, including cancer, infections, inflammation, etc. During this time, many genes have been targeted by specifically engineered agents from different classes of smallmolecule nucleic-acid-based drugs in experimental models of disease to probe, dissect, and characterize further the complex processes that underpin molecular signaling. Subsequently, a number of molecules have been examined in the setting of clinical trials, and several have recently made the successful transition from the bench to the clinic, heralding an exciting era of gene-specific treatments. This is particularly important because clear inadequacies in present therapies account for significant morbidity, mortality, and cost. The broad umbrella of gene-silencing therapeutics encompasses a range of agents that include deoxyribozymes (DNAzymes, Dzs), ribozymes, siRNAs, ASOs, aptamers, and decoys. This chapter tracks

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current movements in these technologies, focusing mainly on Dzs and siRNAs, because these are poised to play an integral role in antigene therapies in the future.
