mRNA医薬品のワクチンを超えた中枢神経系疾患治療への展開

抄録

The success of mRNA vaccines against COVID–19 has sparked mRNA research in various medical applications, such as protein replacement therapy. Given mRNA's efficiency in producing proteins in non–dividing cells, there is a growing focus on developing mRNA therapeutics for central nervous system (CNS) diseases, where a majority of cells are non–dividing. However, delivering mRNA to the CNS poses a significant challenge. Polyplex micelles (PMs) enable safe and efficient mRNA delivery to the CNS through local administration to the cerebrospinal fluid or brain parenchyma. This system has led to notable treatment efficacy for acute CNS conditions, including spinal cord injury and brain ischemia. Additionally, PMs have demonstrated their potential for CRISPR/Cas9–based in vivo genome editing in the brain parenchyma. While local delivery offers efficient outcomes, systemic delivery is a more accessible and less invasive option. Yet, it requires addressing challenges such as enhanced nuclease resistance and the development of mechanisms to cross the blood–brain barriers. Currently, there is ongoing development of PMs tailored for systemic delivery for advancing the treatment landscape for CNS diseases.