Delivery of RNA interference triggers to sensory neurons in vivo using herpes simplex virus.
BACKGROUND
Pain is a hugely important area of research attracting considerable academic and commercial interest. However, the application of RNA interference (RNAi) to the study of nociceptive processes and the development of new analgesics has been limited by the specific challenges associated with the delivery of RNAi triggers to the cell bodies of sensory neurons in the dorsal root ganglia (DRG).


METHODS
In the past five years, delivery of small-interfering RNA (siRNA) to the DRG and spinal cord has achieved effective and specific silencing of targeted genes in various animal models of pain. However, delivery of short-hairpin RNA (shRNA) or artificial microRNA (miRNA) to sensory neurons in vivo has not been feasible using most delivery systems currently available.


RESULTS
Replication-defective vectors based on herpes simplex virus (HSV), which are particularly efficient at targeting DRG neurons, have been recently engineered to express shRNA and artificial miRNA. Whilst silencing induced by siRNA is transient and requires relatively high doses of silencing triggers, HSV-mediated expression of shRNA/miRNA in sensory neurons allows silencing of targeted genes for at least one week following a single injection.


CONCLUSIONS
The potential to use inducible or tissue-specific promoters and to simultaneously silence multiple gene targets, in addition to recent studies suggesting that artificial miRNAs may have improved safety profiles, hold clear advantages for the use of miRNA-based vectors for gene silencing in sensory neurons.
Anesti
Anna-Maria
AM
NeuroVex, BioVex Ltd, Oxfordshire, UK. manesti@biovex.com
Coffin
Robert S
RS
D000818:Animals; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D010146:Pain / Q000235:genetics; D059408:Pain Management; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000378:metabolism*; D018139:Simplexvirus / Q000235:genetics*; D014779:Virus Replication
D035683:MicroRNAs; D034741:RNA, Small Interfering