Intracranial delivery of synthetic mRNA to suppress glioblastoma

Abstract

Owing to messenger RNA's unique biological advantages, it has received increasing attention to be used as a therapeutic, known as mRNA-based gene therapy. It is critical to have an ideal strategy of mRNA gene therapy for glioma, which grows in a special environment. In the present study, we screened out a safe and efficient transfection reagent for intracranial delivery of synthetic mRNA in mouse brain. First, in order to analyze the effect of different transfection reagents on the intracranial delivery of mRNA, the synthetic luciferase mRNA was 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. Then, to test the therapeutic effect of our intracranial delivery mRNA model on glioma, synthetic modified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA was used as an example of therapeutic application. This model demonstrated that synthetic mRNA could be successfully delivered into the brain using commercially available transfection reagents, and TransIT-mRNA showed better results than in vivo -jetPEI kit. This model can be applied in precise targeting and personalized gene therapy of glioma.

Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer

“…However, screens of large libraries have identified few materials that deliver mRNA outside of the liver and spleen ( 8 , 20 – 22 , 34 ). Alternative administration routes can circumvent this issue, as has been demonstrated by our laboratory ( 35 ) and others ( 30 ) for mRNA delivery to organs including the heart ( 36 ), brain ( 37 ), and lungs ( 38 , 39 ). Extrahepatic mRNA delivery can also be achieved by incorporating charged amphipathic phospholipids, which shifts protein expression away from the liver to the spleen or lungs ( 40 – 42 ).…”

Emerging role of vaccines in glioblastoma treatment

“…Figure 1. mRNA vaccines inhibit tumor growth on its size and weight in mice [16] The evaluation of in vitro test from the present study showed TransIT-mRNA injection obtained a longer in vivo half-life and caused little inflammation response than the other, and the optimized dose concentration of 1 μg/20 μL (mRNA/TransIT-mRNA). Additionally, the synthetic red fluorescent protein (RFP) mRNA served as the brain localizer for precise mRNA delivery inside the brain.…”

“…Among all potent DCs (Dendritic cells) electroporated with synthesized mRNA for use in immunotherapy is now the primary reagent chosen to deliver transfection of mRNA as it shows safety in patients with malignancy [13]. The mRNA gene fragment can function on both stationary and proliferating cells without endangering the host cells through translation towards targeting proteins or peptides in the cytoplasm rather than the nuclei.…”

Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases

“…They found that TransIT‐mRNA kit showed the highest TRAIL expression in mice. [ 290 ] Nanomedicines can also serve as the transfection agent to deliver mRNA by an intracerebroventricular administration of Lipid NPs (LNPs) encapsulating luciferase mRNA. Luminometry revealed that the LNPs successfully transfected the cells in the mouse brains.…”