TY - JOUR
T1 - Efficient healing of large osseous segmental defects using optimized chemically modified messenger RNA encoding BMP-2
AU - de la Vega, Rodolfo E.
AU - van Griensven, Martijn
AU - Zhang, Wen
AU - Coenen, Michael J.
AU - Nagelli, Christopher V.
AU - Panos, Joseph A.
AU - Peniche Silva, Carlos J.
AU - Geiger, Johannes
AU - Plank, Christian
AU - Evans, Christopher H.
AU - Balmayor, Elizabeth R.
N1 - Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2022/2
Y1 - 2022/2
N2 - Large segmental osseous defects heal poorly. Recombinant, human bone morphogenetic protein-2 (rhBMP-2) is used clinically to promote bone healing, but it is applied at very high doses that cause adverse side effects and raise costs while providing only incremental benefit. We describe a previously unexplored, alternative approach to bone regeneration using chemically modified messenger RNA (cmRNA). An optimized cmRNA encoding BMP-2 was delivered to critical-sized femoral osteotomies in rats. The cmRNA remained orthotopically localized and generated BMP locally for several days. Defects healed at doses ≥25 μg of BMP-2 cmRNA. By 4 weeks, all animals treated with 50 μg of BMP-2 cmRNA had bridged bone defects without forming the massive callus seen with rhBMP-2. Moreover, such defects recovered normal mechanical strength quicker and initiated bone remodeling faster. cmRNA regenerated bone via endochondral ossification, whereas rhBMP-2 drove intramembranous osteogenesis; cmRNA provides an innovative, safe, and highly translatable technology for bone healing.
AB - Large segmental osseous defects heal poorly. Recombinant, human bone morphogenetic protein-2 (rhBMP-2) is used clinically to promote bone healing, but it is applied at very high doses that cause adverse side effects and raise costs while providing only incremental benefit. We describe a previously unexplored, alternative approach to bone regeneration using chemically modified messenger RNA (cmRNA). An optimized cmRNA encoding BMP-2 was delivered to critical-sized femoral osteotomies in rats. The cmRNA remained orthotopically localized and generated BMP locally for several days. Defects healed at doses ≥25 μg of BMP-2 cmRNA. By 4 weeks, all animals treated with 50 μg of BMP-2 cmRNA had bridged bone defects without forming the massive callus seen with rhBMP-2. Moreover, such defects recovered normal mechanical strength quicker and initiated bone remodeling faster. cmRNA regenerated bone via endochondral ossification, whereas rhBMP-2 drove intramembranous osteogenesis; cmRNA provides an innovative, safe, and highly translatable technology for bone healing.
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U2 - 10.1126/sciadv.abl6242
DO - 10.1126/sciadv.abl6242
M3 - Article
C2 - 35171668
AN - SCOPUS:85124777837
SN - 2375-2548
VL - 8
JO - Science Advances
JF - Science Advances
IS - 7
M1 - eabl6242
ER -