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Tendon healing induced by chemically modified mRNAs

Groth, K and Berezhanskyy, T and Aneja, MK and Geiger, J and Schweizer, M and Maucksch, L and Pasewald, T and Brill, T and Tigani, Bruno and Weber, Eckhard and Rudolph, C and Hasenpusch, G (2017) Tendon healing induced by chemically modified mRNAs. European cells and materials, 33. pp. 294-307. ISSN 1473-2262

Abstract

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 a therapeutic protein, presents itself as an innovative approach addressing tendon healing. In the current study, we demonstrate that injection of naked cmRNA in glucose-containing solution into tendons results in high protein expression in healthy and experimentally injured tendons. Injection of BMP-7 encoding cmRNA resulted in increased BMP-7 protein expression, less fulminant degradation of collagen type I, decreased collagen type III formation as well as trends towards higher collagen I/III ratio and chemotactic cell attraction in surgically dissected tendons compared to vehicle treatment. Moreover reporter protein encoding cmRNA was injected into acute tendon injuries in a highly translational sheep model, revealing wide spread and profound tissue transfection in pathologically affected tissue. Summarizing, these results demonstrate the potential of cmRNAs encoding for therapeutic proteins as a new class of drugs for the treatment of tendon disorders.

Item Type: Article
Keywords: mRNA, tendinopathy, tendon rupture, gene therapy, regenerative medicine, sheep
Date Deposited: 30 Jun 2017 00:45
Last Modified: 30 Jun 2017 00:45
URI: https://oak.novartis.com/id/eprint/24858

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