Delivery systems and therapeutic applications of mRNA targeting the central nervous system

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  • Uchida Satoshi
    Department of Advanced Nanomedical Engineering, Medical Research Institute, Tokyo Medical and Dental University （TMDU） Medical Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Innovation Center of NanoMedicine （iCONM）, Kawasaki Institute of Industrial Promotion

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Other Title
  • 中枢神経系を標的としたmRNA医薬のDDSと治療応用

Abstract

Success in coronavirus infectious disease （COVID）-19 mRNA vaccines is prompting research and development of mRNA therapeutics in various medical fields. Particularly the central nervous system （CNS） has numerous intractable diseases demanding new therapeutic modalities. Proper mRNA delivery systems to the brain are essential for the mRNA-based treatment of CNS diseases. The delivery routes to CNS include local administration to the brain parenchyma and cerebrospinal fluid, systemic delivery across the blood-brain barrier （BBB）, and a nose-to-brain route. Polyplex micelles （PMs） loading mRNA show promise in the local administration, providing efficient protein expression in the broad area of the CNS tissue with minimal inflammatory responses and demonstrating their therapeutic potential in treating CNS diseases. For example, mRNA encoding an antibody fragment targeting amyloid beta reduced amyloid beta burden in the mouse brain after intraventricular delivery using PM. Moreover, in CRISPR/Cas9-based genome editing, PM loading Cas9 mRNA and single guide RNA enabled site-specific genome cleavage in the neurons, astrocytes, and microglia in the mouse brain after intraparenchymal delivery. Meanwhile, local delivery requires arduous and invasive procedures, limiting the target diseases. Thus, mRNA delivery systems for reaching CNS from the blood and nose are under intensive development, which would broaden the target CNS diseases of mRNA therapeutics.

Journal

  • Drug Delivery System

    Drug Delivery System 38 (2), 125-133, 2023-03-25

    THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

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