Development of Pre-Clinical Models for Evaluating the Therapeutic Potential of Candidate siRNA Targeting STAT6
Figure 6
Bio-ditribution of STAT6 targeting siRNA following intranasal delivery.
Fine dissection (f) followed by mRNA and protein analysis, revealed that STAT6 expression within the nasal cavity of Brown Norway rats was invariant (a, b). Anaesthetised animals were administered 2mg/kg of siRNA in sterile saline and bioanalytical analysis performed 72 hours later on fine-dissected tissue samples and plasma. Small interfering RNA was detectable throughout the nasal cavities (<0.1% original dose) with 372m present at significantly higher (P<0.001) levels in the SL compared to 372u (c, d). 372m persisted longer and was detected at significantly higher levels in rat plasma compared to 372u (e). Values presented are mean ± S.E.M (n = 6), and P-value represents comparison to 372u. Nasal sections = Lateral lining, LL; inferior ethmoid turbinate, IE; median ethmoid turbinate, ME; superior ethmoid turbinate, SE; maxilla-turbinate, M; naso-turbinate, N & septum lining, SL.
