title: Knockdown of cortical transthyretin expression around implanted neural prosthetic devices using intraventricular siRNA injection in the brain.
abstract: Neural prosthetic devices are showing increasing clinical use for the treatment of a variety of neurological disorders. However the functions on these devices are often limited due to an inability to effectively and chronically interface with neural tissue. The insertion of devices has been shown to result in significant cellular and vascular trauma surrounding the insertion site. In particular, the up-regulation of genes involved in neuronal degeneration are believed to contribute to the loss of neuronal tissue. RNA interference is a novel technique for the development of antisense therapeutics for the post-transcriptional silencing of specific genes. In order to demonstrate the feasibility of RNA interference for gene-specific silencing in vivo, a short interfering RNA targeting transthyretin, was infused prior to unilateral device insertion. Injection of siRNA was found to significantly reduce the expression of transthyretin mRNA when expression was assessed at 1 week following device insertion. Concomitant decreases in transthyretin protein levels were also observed. These data demonstrate the feasibility of using RNA interference to modulate the initial reactive cellular responses that occur in the brain following insertion of neural prosthetic devices.
authors: Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
authors: Karen L
authors: KL
authors: Smith
authors: Bruce
authors: B
authors: Herron
authors: Natalie
authors: N
authors: Dowell-Mesfin
authors: Hong
authors: H
authors: Wu
authors: Sung June
authors: SJ
authors: Kim
authors: William
authors: W
authors: Shain
authors: Matthew R
authors: MR
authors: Hynd
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000235:genetics* / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics; D011228:Prealbumin / Q000037:antagonists & inhibitors* / Q000235:genetics; D019736:Prostheses and Implants / Q000009:adverse effects*; D034622:RNA Interference / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011228:Prealbumin; D034741:RNA, Small Interfering