Gene therapy is a technique of using genes or nucleic acids to treat or prevent a disease. Gene therapy is a promising treatment for genetic disorders, certain cancers, muscular and neurological disorders. In gene therapy, nucleic acid polymers packaged within a vector are delivered into the cells. These polymers are either expressed as proteins, interfere with protein expression, or possibly correct genetic mutations.
Gene therapy is an important strategy to repair the diseased or damaged cells by genetically regulating the function, especially in neurological disorders like paralysis and Alzheimer’s disease where cell regeneration capacity is impaired. However, conventional gene therapy techniques have limitations. The viral vectors (vehicles) and plasmid DNA administration into the cells has greater risk of accidental mutations in the undamaged parts of the genome. Alternatively, administration of mRNA would be a promising approach for treating neurological disorders because mRNA can provide proteins and peptides in their native forms for mature non-dividing neural cells, without the need of entering their nuclei. However, direct mRNA administration into neural tissues in vivo has been challenging due to very unstable nature of mRNA and its strong immunogenicity.
To address this, a research team led by Associate Prof Keiji Itaka and Prof Kazunori Kataoka from Graduate School of Medicine/Engineering, University of Tokyo, designed a novel nano vehicles or nanomicelles for administration of mRNA in the treatment of sensory nerve disorders. This novel carrier design is based on the self-assembly of polyethylene glycol (PEG)-polyamino acid block copolymer, i.e. polyplex nanomicelles, and applied mRNA. This is the first study to show the therapeutic potential of introducing exogenous mRNA for the treatment of neurological disorders.
Intranasal administration of mRNA-loaded nanomicelles provided efficient, sustained protein expression for nearly two days in nasal tissues, particularly in the lamina propria which contains olfactory nerve fibers, with effectively regulating the immunogenicity of mRNA. Researchers have tested, once-daily intranasal administration of brain-derived neurotrophic factor (BDNF)-expressing mRNA using nanomicelles. This remarkably enhanced the neurological recovery of olfactory function along with repairing the olfactory epithelium to a nearly normal architecture in experimental mouse models. These results indicate the feasibility and safety of using mRNA, and provide a novel strategy of mRNA-based gene therapy.
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