Antisense therapeutics and the treatment of CNS disease.

Antisense oligonucleotides (ONs) have great therapeutic potential for conditions in which aberrant protein production results in pathology. This method of reducing the expression of a target gene is both precise and sequence-specific. Although there are many applications for antisense ONs as central nervous system (CNS) therapeutics, systemically administered antisense ONs must be capable of crossing the blood-brain barrier (BBB) in quantities effective enough to alter protein production in the CNS. Because antisense ONs are large, highly polar molecules, their rate of transport across the BBB is likely to be low. Recent studies have shown that antisense ONs are capable of crossing the BBB without the aid of a carrier system, however little is known about the molecular mechanisms which mediate this transport. This review will focus on nucleic acid chemistries suitable for in vivo research and their potential applications in the treatment of CNS disease.