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. Despite these problems, a number of potential applications of AS-ODNs in CNS therapeutics have been validated in vitro and, in some cases, in vivo. Here the authors outline available nucleic acid chemistries and review progress in the development of non-invasive delivery vehicles that may be applicable to CNS therapeutics. Further to this, they discuss a number of experimental applications of AS-ODNs to CNS research and speculate on the development of antisense techniques to treat CNS disease.
Godfray
Jenny
J
ExpressOn BioSystems Ltd, The Logan Building, Roslin BioCentre, Roslin, Midlothian EH25 9TT, Scotland. jenny@expresson.co.uk
Estibeiro
Peter
P
D000544:Alzheimer Disease / Q000188:drug therapy; D001673:Biodegradation, Environmental; D001932:Brain Neoplasms / Q000188:drug therapy; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy; D016503:Drug Delivery Systems; D015195:Drug Design; D020868:Gene Silencing; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D001523:Mental Disorders / Q000188:drug therapy; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress; D014677:Pharmaceutical Vehicles; D011108:Polymers / Q000008:administration & dosage; D013329:Structure-Activity Relationship
D002491:Central Nervous System Agents; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D014677:Pharmaceutical Vehicles; D011108:Polymers