Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration.

ABSTRACT: Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting the serotonin transporter (SERT). As a result, ~80% of patients show recurrent or chronic depression, resulting in a poor quality of life and increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used to evoke antidepressant-like responses in experimental animals. However, the main limitation for the medical use of RNAi is the extreme difficulty to deliver oligonucleotides to selected neurons/systems in the mammalian brain. Here we show that the intranasal administration of a sertraline-conjugated small interfering RNA (C-SERT-siRNA) silenced SERT expression/function and evoked fast antidepressant-like

SUBMITTER: Ferres-Coy A 

PROVIDER: S-EPMC4759205 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature