CHAPTER 20: Preclinical and Clinical Drug-metabolism, Pharmacokinetics and Safety of Therapeutic Oligonucleotides

During the past decade, therapeutic oligonucleotide drugs (OND) have witnessed a tremendous progression that has translated into an increasing number of successful clinical applications. We now have a better understanding of the molecular mechanisms critical to efficacy, distribution and toxicity and how these are affected by OND sequence, chemical modifications and design. The current overview summarizes key drug-metabolism and pharmacokinetics and toxicological aspects of OND therapeutics and how these properties are influenced by OND design and chemistry, with a focus on new knowledge obtained in the past decade.