Antisense oligonucleotides - the way forward

Abstract

Antisense oligonucleotides provide attractive possibilities for developing a new class of drugs and the design principle involves straightforward base-pairing rules. The approach has already been useful in many functional genomics efforts and there has also been recent clinical success. With this progress in place, it now is appropriate to thoroughly address design uncertainties and unforeseen effects that have emerged. The key objective has long been, and remains to be, the identification of novel oligonucleotide analogs providing the possibility of achieving high in vivo efficacy in the absence of significant toxicity; such compounds are not at hand today but certain advances have been made in recent years. There is also a need for more expertise in target site selection and for improving delivery and/or bioavailability properties. Immediately achievable goals in the field implicate use of improved in vitro and in vivo assays and, importantly, a set of standard controls, uniform between laboratories, such that results can be compared in a rational manner. In turn, this should lead to the emergence of antisense agents that are useful for a wide range of research and therapeutic applications.