Improved brain expression of anti-amyloid β scFv by complexation of mRNA including a secretion sequence with PEG-based block catiomer
Résumé
Amyloid β aggregates have been proposed as central effectors in Alzheimer's disease, with several passive immunization clinical trials. We used mRNA encoding oligomer-specific anti-amyloid β (Aβ) scFv for passive immunotherapy. These scFvs could recognize amyloid oligomers with significant affinity, delay the aggregation of amyloid β in vitro, and dissociate Aβ aggregates in vitro. Intra-cerebroventricular injection of pDNA and mRNA encoding the scFv resulted in detectable scFv levels in the brain, with higher in vivo expression from mRNA. Notably, injection of mRNA decreased Aβ burden in an acute amyloidosis model. scFv production in situ from mRNA represents a novel immunotherapy approach, and a safer alternative compared to the administration of anti-Aβ antibodies or adenovirus encoding antibodies.
Domaines
Chimie thérapeutique| Origine | Fichiers produits par l'(les) auteur(s) |
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