期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 16, 期 -, 页码 162-171出版社
CELL PRESS
DOI: 10.1016/j.omtn.2019.02.012
关键词
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资金
- JSPS KAKENHI [JP15H03017]
- Center of Innovation (COI) Program (Center of Open Innovation Network for Smart Health) from the Japan Science and Technology Agency (JST)
- JSPS Core-to-Core Program, A. Advanced Research Networks
- JSPS Postdoctoral Fellowship for Foreign Researchers [26.04406]
- Ministry of Science and Technology (MOST), Taiwan [MOST 106-2314-B-039-053, MOST 107-2314-B-039-023, MOST 107-2622-E-039-003, CMU106-N-18]
- China Medical University (CMU), Taiwan [MOST 106-2314-B-039-053, MOST 107-2314-B-039-023, MOST 107-2622-E-039-003, CMU106-N-18]
Intervertebral disk (IVD) degeneration is often associated with severity of lower back pain. IVD core is an avascular, highly hydrated tissue composed of type II collagen, glycosaminoglycans, and proteoglycans. The disk degeneration is not only a destruction of IVD structure but also is related to a disorder of the turnover of the disk matrix, leading the jelly-like IVD core to be replaced by fibrous components. Here we present a disease-modifying strategy for IVD degenerative diseases by direct regulation of the cells in the IVD using mRNA medicine, to alter the misbalanced homeostasis during disk degeneration. When mRNA encoding a cartilage-anabolic transcription factor, runt-related transcription factor-1, was administered to a rat model of coccygeal disk degeneration using a polyplex nanomicelle composed of polyethylene glycol-polyamino acid block copolymers and mRNA, the disk height was maintained to a significantly higher extent (approximate to 81%) compared to saline control (69%), with prevention of fibrosis in the disk tissue. In addition, the use of nanomicelles effectively prevented inflammation, which was observed by injection of naked mRNA into the disk. This proof-of-concept study revealed that mRNA medicine has a potential for treating IVD degenerative diseases by introducing a cartilage-anabolic factor into the host cells, proposing a new therapeutic strategy using mRNA medicine.
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