BITAM Research Project
Project summary
Partners of BITAM pioneered the use of mRNA for bone healing purposes. The development of a stabilized, non-immunogenic mRNA encoding BMP-2 (BMP-2 SNIM®RNA). Experiments involving the transfection of cells with BMP-2 SNIM®RNA showed that the use of the cmMRNA may be well suited to the physiological needs of bone healing in vivo. After years of mRNA construct design and optimization, partners of BITAM were able to produce a highly osteogenic, non-toxic BMP-2 SNIMⓇRNA that indeed showed low immunogenicity in vitro. The technology was patented and the results obtained using the drug have since been published. Through studies focused on investigating the ability of the compound to heal non-union bone defect they have shown that not only did the BMP-2 SNIM®RNA heal the bone defects, but it also resulted in a regenerate explant with superior biomedical performance. It was also demonstrated that administered BMP-2 SNIM®RNA remained local with the non-union bone defect without leakage into the circulation or to vital organs.
Diverse biomaterials including fibrin and fibrinogen, calcium phosphate ceramics, bioactive glass, and poly-D,L-lactic acid as matrix for BMP-2 SNIM®RNA were studied by BITAM consortium. The outcome showed strong advantages in combining the mRNA with 3D biomaterials. Recently, it has been proven that compatibility exists between BMP-2 SNIM®RNA and medical grade PCL-TCP bioresorbable biomaterial. The material dissolves over time, leaving only natural, healthy bone. For the project mgPCL-TCP scaffolds will be fabricated by vendor Osteopore (SG), the leading global company in manufacturing this type of product. With over 20 years of experience in designing, developing, and marketing bioresorbable polymer implants for orthopedic surgery, our vendor’s proprietary technology has been FDA- and EU-approved and used in 80,000 patients to heal bone. Collectively, the preclinical data amassed by the BITAM consortium over many years of pioneering research has provided preclinical proof of principle concerning the ability of RNA-based technology to heal non-union bone fractures. The goal of this project is to bring this state-of-the-art technology into TRL 6. Which will allow immediate translation into human clinical studies. The project proposes to answer the following: Can SNIMplant, a combination of BMP-2 SNIM®RNA with an additive-manufactured bioresorbable mgPCL-TCP implant, heal non-union fractures in clinically relevant animal models?
Partners
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Experimental Orthopaedics and Trauma Surgery, RWTH Aachen University Hospital (Scientific coordinator)
Experimental Orthopaedics and Trauma Surgery
RWTH Aachen University Hospital
(Scientific coordinator)Team
Project leader
Prof. Dr. Elizabeth Rosado Balmayor, Ph.D.
Cja
RWTH Aachen University Hospital
Pauwelsstraße 17
D-52074 Aachen Germany
Phone: +49-241-80-89727
E-mail: erosadobalma@ukaachen.de
ORCID: 0000-0002-0484-4847
X: @er_balmayor
http://linkedin.com/in/elizabeth-rosado-balmayor-0726504a
Project team member
Gabriella Rios, M.Sc.
Ph.D. candidate
RWTH Aachen University Hospital
Pauwelsstraße 17
D-52074 Aachen
Germany
Phone: +49-241-80-89727
E-mail: grios@ukaachen.de
ORCID: 0009-0006-0466-8800
http://linkedin.com/in/gabriella-rios-aa507829bPartner’s role in the project:
Experimental Orthopaedics and Trauma Surgery at RWTH University Hospital Aachen serves as the scientific coordinating and translational partner of the BITAM project, responsible for assembling, validating, and advancing SNIMplant toward clinical readiness. RWTH Aachen subcontracts the GMP production of the bioresorbable mgPCL-TCP scaffold to Osteopore, combines this implant with Ethris’ BMP-2 SNIM®RNA to manufacture the final SNIMplant product, and performs comprehensive quality control, biocompatibility, and bioactivity testing. RWTH Aachen leads all in-vitro functionality studies, oversees and supplies SNIMplant for in-vivo preclinical studies across multiple animal models. In addition, RWTH Aachen manages regulatory strategy, project coordination, risk management, and dissemination, ensuring compliance with international standards and guiding the technology to TRL-6 and readiness for first-in-human clinical studies.
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ETHRIS GmbH
ETHRIS GmbH
Team
Prof. Dr. Christian Plank, Ph.D.
Managing Director
Chief Technology Officer
Ethris GmbH
Semmelweisstrasse 3
D-82152 Planegg
www.ethris.com
Phone: +49(0)89895578812
E-mail: plank@ethris.com
ORCID: 0000-0002-6072-4903
http://linkedin.com/in/christian-plank-6499914
Dr. Christian Dohmen, Ph.D.
Executive Director, Technology Development & CMC
Ethris GmbH
Semmelweisstrasse 3
D-82152 Planegg
www.ethris.com
Phone: +49(0)898955788-283
E-mail: dohmen@ethris.com
http://linkedin.com/in/christian-dohmen-9366293bPartner’s role in the project:
Ethris GmbH is a German SME pioneering the next-generation mRNA therapeutics using its proprietary SNIM®RNA and SNaP LNP® platforms. Ethris is the BITAM partner responsible for developing and producing the biologically active drug component of SNIMplant, namely the BMP-2 SNIM®RNA. Ethris designs and optimizes the stabilized, non-immunogenic BMP-2 mRNA (including proprietary 5′-UTR optimization to enhance protein expression at low doses), manufactures it via in-vitro transcription using chemically modified nucleotides, and formulates it into its clinically validated proprietary lipidoid nanoparticle system to enable efficient cellular delivery. Ethris also performs comprehensive quality control and bioactivity testing and supplies technical-grade BMP-2 SNIM®RNA-LNPs for all BITAM preclinical studies, while retaining worldwide intellectual property for the SNIM®RNA and formulation technologies that underpin the project’s translational and clinical potential.
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Mayo Clinic
Mayo Clinic
Team
Prof. Dr. Christopher H. Evans, Ph.D., D.Sc., FLSW
Director, Rehabilitation Medicine Research Center
Director, Musculoskeletal Gene Therapy Laboratory
Mayo Clinic
200 First Street S.W.
Rochester, MN 55905
www.mayoclinic.org
E-mail: evans.christopher@mayo.edu
Dr. Rodolfo de la Vega Amador, M.D., Ph.D.
Assistant Professor, Orthopedic Surgery & Physical Medicine and Rehabilitation
Associate Consultant, Orthopedic Surgery
Mayo Clinic
200 First Street S.W.
Rochester, MN 55905
www.mayoclinic.org
Phone: +1-507-266-0436
E-mail: delavega.rodolfo@mayo.edu
http://linkedin.com/in/rodolfo-de-la-vega-28474951Partner’s role in the project:
Mayo Clinic (USA) is responsible for independently validating the bone-healing efficacy of SNIMplant in a well-established and clinically relevant small-animal model. Within the BITAM project, Mayo Clinic conducts the rat critical-sized femoral defect study, using its long-standing expertise in gene and RNA-based therapies for bone regeneration. Mayo evaluates SNIMplant’s ability to heal non-union fractures through longitudinal imaging (X-ray, micro-CT) and post-mortem histological and biomechanical analyses, thereby providing robust, independent preclinical evidence that the technology effectively induces bone regeneration before progression to larger animal models and clinical translation.
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AO Research Institute Davos, ARI
AO Research Institute Davos, ARI
Team
Prof. Martin Stoddart, Ph.D., FRSB, FIOR
Program Leader – Regenerative Orthopaedics, Principal Scientist
Vice-Director
AO Research Institute Davos
Clavadelerstrasse 8
7270 Davos, Switzerland
Phone: +41 81 414 24 48
E-mail: martin.stoddart@aofoundation.org
ORCID: 0000-0002-9538-1517
http://linkedin.com/in/prof-martin-stoddart-phd-0461a011
Dr. Stephan Zeiter, Dr. med. vet., Ph.D.
Program Leader – Preclinical Services
Focus Area Leader – Surgery
AO Research Institute Davos
Clavadelerstrasse 8
7270 Davos, Switzerland
Phone: +41 81 414 23 11
E-mail: stephan.zeiter@aofoundation.org
ORCID: 0000-0002-8155-4202
https://www.linkedin.com/in/stephan-zeiter-a0618689Partner’s role in the project:
The team at AO Research Institute Davos, ARI, contributes both preclinical and translational expertise to the BITAM consortium. ARI evaluates the innovative SNIMplant in a large-animal sheep model, performing surgical implantation, post-operative care, and comprehensive monitoring of bone healing via radiography, in vivo CT, micro-CT, and histology to provide critical preclinical evidence of efficacy. The work of the ARI team in BITAM is crucial to ensure translation of the BITAM innovative technology to first-in-human clinical studies.
Related Publications
Del Toro Runzer, C.; van Griensven, M.; Balmayor, E. R. Engineering bone tissue with mRNA: from molecular design and delivery to clinical applications. Materials Today 2025, 91, 124–147, doi; 10.1016/j.mattod.2025.11.002
Del Toro Runzer, C.; Balmayor, E. R.; van Griensven, M. Biologics for Bone Regeneration: Advances in Cell, Protein, Gene, and mRNA Therapies. Bone Research 2025, 4(1), 5, doi; 10.1038/s41413-025-00487-0
Del Toro Runzer, C.; Sadowska, J. M.; Roumans, N.; Plank, C.; Evans, C. H.; O’Brien, F. J.; van Griensven, M.; Balmayor, E. R. Synergistic Osteogenesis After Co-Administration of cmRNAs Encoding BMP-2 and BMP-7 Utilizing a Transcript-Activated Matrix. Advanced Functional Materials 2025, e08631, doi: 10.1002/adfm.202508631.
Del Toro Runzer, C.; Plank, C.; van Griensven, M.; Balmayor, E. R. Inside the cell: Approaches to evaluating mRNA internalization and trafficking. Methods 2025, 241: 173-183. doi: 10.1016/j.ymeth.2025.06.006. PMID: 40513751
van der Heide, D.; Del Toro Runzer, C.; Della Bella, E.; Plank, C.; van Griensven, M.; Balmayor, E. R.; Stoddart, M. J.; D'Este, M. Implementing BMP-7 Chemically Modified RNA for Bone Regeneration with 3D Printable Hyaluronic Acid-Collagen Granular Gels. Advanced Healthcare Materials 2025, 14(19): e2405047. doi: 10.1002/adhm.202405047. PMID: 40465277.
Del Toro Runzer, C.; Anand, S.; Mota, C.; Moroni, L.; Plank, C.; van Griensven, M.; Balmayor, E. R. Cellular uptake of modified mRNA occurs via caveolae-mediated endocytosis, yielding high protein expression in slow-dividing cells. Molecular Therapy – Nucleic Acids 2023, 32, 960-979. doi: 10.1016/j.omtn.2023.05.019. PMID: 37305166
De La Vega, R. E.; van Griensven, M.; Zhang, W.; Coenen, M. J.; Nagelli, C. V.; Panos, J. A.; Peniche Silva, C. J.; Geiger, J.; Plank, C.; Evans, C. H.; Balmayor, E. R. Efficient healing of large osseous segmental defects using optimized chemically modified messenger RNA encoding BMP-2. Science Advances 2022, 8(7): eabl6242. doi: 10.1126/sciadv.abl6242. PMID: 35171668.
Balmayor, E. R. Synthetic mRNA – emerging new class of drug for tissue regeneration. Current Opinion in Biotechnology 2021, 75:8-14. doi: 10.1016/j. copbio.2021.10.015. PMID: 34749063.
De la Vega, R. E.; Atasoy-Zeybek, A.; Panos, J. A.; van Griensven, M.; Evans, C. H.; Balmayor, E. R. Gene therapy for bone healing: lessons learned and new approaches. Translational Research 2021, 236:1-16. doi: 10.1016/j.trsl.2021.04.009. PMID: 33964474
Omnia, F.; van Griensven, M.; Tahmasebi Birgani, Z.; Plank, C.; Balmayor, E. R. Transcript-activated Coatings on Titanium Mediate Cellular Osteogenesis for Enhanced Osteointegration. Molecular Pharmaceutics 2021, 18(3): 1121-1137. doi: 10.1021/acs.molpharmaceut.0c01042. PMID: 33492959
De la Vega, R. E.; Evans, C. H.; van Griensven, M.; Balmayor, E. R. Healing with RNA. Injury. 2019, 50(3):625-626. doi: 10.1016/j.injury.2019.03.036. PMID: 31005241
Balmayor, E. R.; Evans, C. H. RNA Therapeutics for Tissue Engineering. Tissue Engineering Part A 2019, 25(1-2): 9-11. doi: 10.1089/ten.TEA.2018.0315. PMID: 30426843
Zhang, W.; De La Vega, R. E.; Coenen, M. J.; Peniche Silva, M. J.; Aneja, M. K.; Plank, C.; van Griensven, M.; Evans, C. H.; Balmayor, E. R. An improved, chemically modified RNA encoding BMP-2 enhances osteogenesis in vitro and in vivo. Tissue Engineering Part A 2019, 25(1-2): 131-144. doi: 10.1089/ten.TEA.2018.0112. PMID: 30009674
Balmayor, E.R.; Geiger, J.P.; Koch, C.; Aneja, M.K.; van Griensven M.; Rudolph, C.; Plank, C. Modified mRNA for BMP 2 in combination with biomaterials serves as a transcript activated matrix for effectively inducing osteogenic pathways in stem cells. Stem Cells and Development 2017, 26(1): 25-34. doi: 10.1089/scd.2016.0171. PMID: 27676276
Ferizi, M.; Aneja, M.K.; Balmayor, E.R.; Badieyan, Z.S.; Mykhaylyk, O.; Rudolph, C.; Plank, C. Human cellular CYBA UTR sequences increase mRNA translation without affecting the half-life of recombinant RNA transcripts. Scientific Reports 2016, 6: Article number 39149. doi: 10.1038/srep39149. PMID: 27974853
Balmayor, E. R.; Geiger, J. P.; Aneja, M. K.; Berezhanskyy, T.; Utzinger, M.; Mykhaylyk, O.; Rudolph, C.; Plank, C. Chemically modified RNA induces osteogenesis of stem cells and human tissue explants as well as accelerates bone healing in rats. Biomaterials 2016, 87: 131-146. doi: 10.1016/j.biomaterials.2016.02.018. PMID 26923361
Jarzębińska, A., Pasewald, T., Lambrecht, J., Mykhaylyk, O., Kümmerling, L., Beck, P., Hasenpusch, G., Rudolph, C., Plank, C., Dohmen, C. A Single Methylene Group in Oligoalkylamine-Based Cationic Polymers and Lipids Promotes Enhanced mRNA Delivery. Angewandte Chemie, International Edition in English 2016, 55(33): 9591-5. doi: 10.1002/anie.201603648