An Improved, Chemically Modified RNA Encoding BMP-2 Enhances Osteogenesis In Vitro and In Vivo

  • Tissue Eng Part A. 2019 Jan;25(1-2):131-144. doi: 10.1089/ten.TEA.2018.0112.
Wen Zhang  1  2 Rodolfo E De La Vega  3 Michael J Coenen  3 Sebastian A Müller  3  4 Carlos J Peniche Silva  1 Manish K Aneja  5 Christian Plank  2  5 Martijn van Griensven  1  3 Christopher H Evans  3 Elizabeth R Balmayor  1  3
Affiliations
  • 1. 1 Department of Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
  • 2. 2 Institute of Molecular Immunology and Experimental Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
  • 3. 3 Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota.
  • 4. 4 Department of Orthopedic Surgery, University of Basel, Basel, Switzerland.
  • 5. 5 Ethris GmbH, Planegg, Germany.
Abstract

The use of chemically modified RNA (cmRNA) with increased stability using translation initiator of short untranslated regions (TISU) offers the prospect of finally allowing us to unlock the potent osteogenic properties of BMP-2 in a clinically expedient manner. As noted, delivery of recombinant BMP-2 protein has had modest clinical efficacy, whereas gene delivery is effective but very difficult to translate into human clinical use. This study shows the great potential of cmRNA encoding BMP-2 with TISU in a long-bone critical-sized rat model.

Keywords
BMP-2; bone healing; mRNA; modified mRNA; transcript therapy; vascularization.
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