Antisense Oligonucleotides and RNA Interference

Kher, Gitanjali; Trehan, Sonia; Misra, Ambikanandan

This chapter outlines the progress made to meet delivery challenges and the clinical applications of antisense technology and highlights the limitations of antisense agents in therapeutics. Antisense technology presents an opportunity to manipulate gene expression within cells to treat an endless number of diseases and is a powerful tool for studying gene function. The antisense approach utilizes antisense agents to fight various diseases by regulating the expression of a specific factor, the presence of which actually causes the particular disease. Liposomes, polyconjugates, and other biodegradable polymeric carriers have emerged as the leading platform for the systemic delivery of RNA interference (RNAi) therapeutics and offer considerable promise for diseases of the liver, solid cancers, as well as potentially enhanced vaccines, infectious diseases, and immune cell-related disorders. This chapter surveys the agents employed in antisense technologies and discusses the various mechanisms of gene silencing. It focuses on those techniques that employ oligonucleotides composed of both modified and unmodified DNA or RNA nucleotides, and on RNAi.