Intracranial Delivery of Synthetic mRNA Using Common Transfection Reagent

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background:</jats:bold> Owing to messenger RNA’s unique biological advantages, it has received increasing attention to be used as a therapeutic gene carrier, known as mRNA-based gene therapy. It is critical to precisely deliver specific mRNA into targeted part of the body to achieve effective treatment.<jats:bold>Methods:</jats:bold> In the present study, a mouse model of intracranial delivery of synthetic mRNA was established using commonly used transfection reagent. Synthetic luciferase mRNAs were wrapped with two different transfection reagents and microinjected into the brain at the fixed point. The expression status of delivered mRNA was monitored by a small animal imaging system. The possible reagent-induced biological toxicity was evaluated by behavioral and blood biochemical measurements. Synthetic modified TRAIL mRNA was also used as an example of therapeutic application.<jats:bold>Results:</jats:bold> This model demonstrated that synthetic mRNA could be successfully delivered into the brain with commonly used transfection reagents without measurable toxicity. The expression of exogenous mRNA persisted in a reasonable period following intracranial injection.<jats:bold>Conclusions:</jats:bold> This mouse model of intracranial delivery of synthetic mRNA can be applied in preclinical studies of mRNA-based gene therapy.</jats:p>