Systemic delivery of therapeutics to neuronal tissues: a barrier modulation approach.

IMPORTANCE OF THE FIELD: Efficient systemic delivery of low-molecular-mass therapeutics to neuronal tissue remains a central issue not only to drug development but also to the chronic treatment of a range of neurodegenerative disorders. AREAS COVERED IN THIS REVIEW: This review discusses the potential of using RNA interference to modulate tight junction proteins at the blood-brain barrier and inner blood-retina barrier. Both systemic delivery of short-interfering RNA and viral-mediated delivery of short hairpin RNA are discussed, highlighting the therapeutic area relevant to each. WHAT THE READER WILL GAIN: Readers will gain an insight into the potential of size-selective and reversible modulation of neuronal barriers and the types of low-molecular-mass molecule that could be used in the treatment of various neurodegenerative or neuromalignant disorders. TAKE HOME MESSAGE: The purpose of this review is to describe a new therapeutic strategy for systemic delivery of low-molecular-mass therapeutics to neuronal tissues.