TENDON HEALING INDUCED BY CHEMICALLY MODIFIED MRNAS
TENDON HEALING INDUCED BY CHEMICALLY MODIFIED MRNAS
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DOI：
10.22203/ecm.v033a22
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发表时间：
2017-01-01
影响因子：
3.1
通讯作者：
Hasenpusch, G.
中科院分区：
文献类型：
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作者：
Groth, K.;Berezhanskyy, T.;Hasenpusch, G.
肌腱疾病在人类和兽医学中都很常见，具有很高的再损伤率和不令人满意的治疗效果。应用编码治疗性蛋白质的裸露化学修饰 mRNA (cmRNA) 是解决肌腱愈合问题的创新方法。在当前的研究中，我们证明将在含葡萄糖溶液中稀释的裸cmRNA注射到肌腱中会导致健康和实验损伤肌腱中的高蛋白表达。与载体对照相比，注射骨形态发生蛋白 7 (BMP-7) 编码 cmRNA 导致 BMP-7 蛋白表达显着升高，并减少 III 型胶原蛋白的形成。此外，在大型动物模型中，不仅在健康肌腱中，而且在实验损伤、严重发炎的肌腱中都可以检测到报告蛋白的表达。总而言之，这些结果证明了编码治疗性蛋白质的 cmRNA 作为一类治疗肌腱疾病的新药物的潜力。
Tendon disorders are frequent both in human and veterinary medicine with high re-injury rates and unsatisfactory therapeutic treatments. Application of naked, chemically-modified mRNA (cmRNA), encoding for therapeutic proteins, is an innovative approach to address tendon healing. In the current study, we demonstrated that injection of naked cmRNA, diluted in a glucose-containing solution, into tendons resulted in high protein expression in healthy and experimentally-injured tendons. Injection of bone morphogenetic protein 7 (BMP-7)-encoding cmRNA resulted in a significantly higher expression of BMP-7 protein and reduced formation of collagen type III, compared to vehicle control. Moreover, in a large animal model, reporter protein expression was detectable not only in healthy, but also in experimentally-injured, severely inflamed tendons. Summarising, these results demonstrated the potential of cmRNAs encoding for therapeutic proteins as a new class of drugs for the treatment of tendon disorders.