期刊
JOURNAL OF CONTROLLED RELEASE
卷 239, 期 -, 页码 137-148出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.08.037
关键词
Chemically modified mRNA (cmRNA); Transcript-activated matrix (TAM); Sustained delivery; Bone regeneration; Human bone morphogenetic protein 2 (hBMP-2); Transcript therapy
资金
- German Federal Ministry of Education and Research Go-Bio grant [0315986]
- Deutsche Forschungsgemeinschaft (DFG) via Excellence Cluster Nanosystems Initiative Munich (NIM) [EXC 4/3]
Transcript therapies using chemically modified messenger RNAs (cmRNAs) are emerging as safe and promising alternatives for gene and recombinant protein therapies. However, their applications have been limited due to transient translation and relatively low stability of cmRNAs compared to DNA. Here we show that vacuum-dried cmRNA-loaded collagen sponges, termed transcript activated matrices (TAMs), can serve as depots for sustained delivery of cmRNA. TAMs provide steady state protein production for up to six days, and substantial residual expression until 11 days post transfection. Another advantage of this technology was nearly 100% transfection efficiency as well as low toxicity in vitro. TAMs were stable for at least 6 months at room temperature. Human BMP-2-encoding TAMs induced osteogenic differentiation of MC3T3-E1 cells in vitro and bone regeneration in a non-critical rat femoral bone defect model in vivo. In summary, TAMs are a promising tool for bone regeneration and potentially also for other applications in regenerative medicine and tissue engineering. (C) 2016 Elsevier B.V. All rights reserved.
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