Is HSV-vector-mediated miRNA expression in dorsal root ganglia stable?

Question

My question is on the following article: "*[Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy](http://molecularpain.biomedcentral.com/articles/10.1186/1744-8069-8-17)*"My question is, do you think the rats continued to have decreased levels of voltage-gated Na⁺ channels after this experiment, or did they likely gain them back up eventually, because dorsal root ganglion neurons regenerate themselves? I couldn't find this info in the article.

Answer 1

Hello, thanks for the question. Typically, any type of knockdown is transient -- it only works so long as the construct is supplied. In vertebrate systems, this is usually shRNA. However, once the construct is "used up", expression should eventually return to normal. How long this takes depends on several factors, including the normal "turn over" of that gene product (assuming it's a protein coding gene), cell type, age, and other factors. However, miRNAs are regulated transcripts and have "reading frames" just like protein coding sequences. Once you get the construct into a cell, along with it's regulatory elements, the expression could remain stable indefinitely, hypothetically. Furthermore, herpes simplex viruses hide out in dorsal root gangia to avoid immune system (this is why people who develop Shingles do so in arcs across their body; the infection is following the innervation pattern of spinal nerves from those particular dorsal ganglia). So, if you new the sequence of an miRNA that knocked down the expression of your favorite gene, and you new the regulatory sequences of this miRNA, all you would need to do is get it into a system that never goes away -- hooray for herpes!