Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration
Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration
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DOI：
10.1016/j.jconrel.2016.08.037
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发表时间：
2016-10-10
影响因子：
10.8
通讯作者：
Plank, Christian
中科院分区：
文献类型：
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作者：
Badieyan, Zohreh Sadat;Berezhanskyy, Taras;Plank, Christian
使用化学修饰的信使RNA（cmRNA）的转录物疗法正在成为基因和重组蛋白疗法的安全且有前景的替代方案。然而，由于瞬时翻译和与DNA相比相对较低的稳定性，它们的应用受到限制。在这里，我们表明，真空干燥的cmRNA加载胶原海绵，称为转录激活基质（TAM），可以作为仓库持续交付的cmRNA。TAM提供稳定状态的蛋白质生产长达6天，并且直到转染后11天都有大量的残余表达。该技术的另一个优点是几乎100%的转染效率以及体外低毒性。TAM在室温下可稳定至少6个月。编码人BMP-2的TAM在体外诱导MC 3 T3-E1细胞的成骨分化，在体内诱导非临界大鼠股骨骨缺损模型中的骨再生。总之，TAM是骨再生的有前途的工具，也可能用于再生医学和组织工程中的其他应用。(C)2016爱思唯尔B. V.保留所有权利。
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.