Treatment of Intervertebral Disk Disease by the Administration of mRNA Encoding a Cartilage-Anabolic Transcription Factor.
RUNX1
intervertebral disk disease
mRNA
mRNA medicine
polyplex nanomicelle
runt-related transcription factor-1
transcription factor
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
07 Jun 2019
07 Jun 2019
Historique:
received:
06
01
2019
revised:
10
02
2019
accepted:
16
02
2019
pubmed:
20
3
2019
medline:
20
3
2019
entrez:
20
3
2019
Statut:
ppublish
Résumé
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 (≈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.
Identifiants
pubmed: 30889482
pii: S2162-2531(19)30042-3
doi: 10.1016/j.omtn.2019.02.012
pmc: PMC6424144
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
162-171Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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