The use of nucleic acid tools for target validation in central nervous system therapy.

The main challenge facing target validation today comes from the ongoing genomics revolution, which is generating an unprecedented number of potential targets. Existing technologies, such as mouse knockouts, are struggling to provide the throughput now required. Nucleic acid tools including antisense, RNA interference, ribozymes and aptamers offer a potentially higher throughput means of manipulating gene expression and thus validating targets in complex biological systems such as the central nervous system.

The potential of antisense as a CNS therapeutic.

Antisense offers a precise and specific means of knocking down expression of a target gene, and is a major focus of research in neuroscience and other areas. It has application as a tool in gene function and target validation studies and is emerging as a therapeutic technology in its own right. It has become increasingly obvious, however, that there are a number of hurdles to overcome before antisense can be used effectively in the CNS, most notably finding suitable nucleic acid chemistries and an effective delivery vehicle to transport antisense oligonucleotides (AS-ODNs) across the blood-brain barrier (BBB) to their site of action.