Groth K, Berezhanskyy T, Aneja M K, Geiger J, Schweizer M, Maucksch L, Pasewald T, Brill T, Tigani B, Weber E, Rudolph C, Hasenpusch G
Ethris GmbH, Semmelweisstr. 3, 82152 Planegg,
Eur Cell Mater. 2017 May 24;33:294-307. doi: 10.22203/eCM.v033a22.
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.
肌腱疾病在人类医学和兽医学中都很常见，其再损伤率高且治疗效果不尽人意。应用编码治疗性蛋白质的裸露化学修饰mRNA（cmRNA）是一种解决肌腱愈合问题的创新方法。在本研究中，我们证明将稀释于含葡萄糖溶液中的裸露cmRNA注射到肌腱中，可在健康和实验性损伤的肌腱中实现高蛋白表达。与载体对照相比，注射编码骨形态发生蛋白7（BMP-7）的cmRNA可使BMP-7蛋白表达显著升高，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，而且在实验性损伤的严重炎症肌腱中都可检测到报告蛋白表达。总之，这些结果证明了编码治疗性蛋白质的cmRNAs作为治疗肌腱疾病的新型药物的潜力。
