In vitro transport and delivery of antisense oligonucleotides.

Publisher Summary In most cell culture studies, free antisense oligonucleotides are initially ineffective and only become active in the presence of an appropriate facilitator or delivery agent. It may be possible to attain antisense effects without a delivery agent by utilizing high concentrations of stable oligonucleotides, but this is the exception rather than the rule. A number of approaches have been used to enhance the cytoplasmic and nuclear delivery of antisense oligonucleotides. These are discussed individually in this chapter. However, there is clearly a need for improved technologies for enhancing the delivery and pharmacological effectiveness of oligonucleotides. For example, many of the agents currently used in laboratory studies are unsuited to in vivo application: they are too toxic, they form very large complexes that would be cleared from the circulation, or they are not able to function in the presence of plasma proteins. It has been quite difficult to identify improved delivery agents for oligonucleotides; one problem has been that many of the assays for antisense activity are arduous. A major issue then is the development and use of appropriate screens to evaluate agents or strategies designed to enhance antisense delivery and therapeutic effects.