Fig. 1: Immune cells infected with miRNA-attenuated JEV viral particles facilitate easier delivery across barriers.
From: Programmable self-replicating JEV nanotherapeutics redefine RNA delivery in ALS
Intravenous administration of miRNA-modified viral particles carrying ASO presents a promising therapeutic strategy for ALS. Upon introduction, the viral particles activate the host’s innate immune system, recruiting immune cells such as dendritic cells and macrophages. These immune cells engulf the viral particles, aiding their migration across the blood-brain and blood-spinal cord barriers. Once within the CNS, the infected immune cells release miRNA-attenuated viral particles, which specifically target motor neurons and other bystander cells. Upon infection, the viral particles release ASOs that inhibit the translation of pathogenic mRNA, particularly mutated SOD1, thus reducing neuronal damage. This targeted delivery system effectively addresses ALS progression by leveraging the neuron-specific infectivity of JEV.
