mRNA-Based Therapy for Osteogenesis
mRNA-based therapy has shown great promise in accelerating bone regeneration (in case of osteoporosis and bone defect) and other diseases. mRNA-based therapy accelerates bone regeneration in a positive regulation by delivering mRNA encoding growth factors. Compared to plasmid DNA (pDNA) therapy, another gene therapy that has been widely investigated for decades, mRNA-based therapy presents more efficiency in hard-to-transfect cells (including primary osteoblasts) due to them exert the function in the cytoplasm. Here, we give a brief introduction to mRNA-based therapeutics for osteogenesis. Besides, to assist the mRNA-based therapy for osteogenesis, Creative Biogene is offering a wide series of mRNA research services.
The therapy development of osteogenesis
The human bone is a complex and dynamic tissue, which has a strong regenerative capacity that is able to restore its structure and function after damage. However, the regeneration of bone tissue still requires additional treatments (including the requirement of bone substitute materials and bone grafts) when the situation that its regenerative capacity is compromised by degenerative bone diseases and large formation of bone defects. In addition to the use of man-made bone substitute materials, such as metal implants, calcium phosphate bioceramics, and polymeric fillers, native bone grafts containing a number of osteogenic factors are extensively investigated to enhance bone regeneration together. Consequently, a broad range of bioactive molecules has been proposed as candidate therapeutics, including hormones, statins, and anti-osteoclastic drugs. Among them, osteogenic growth factors (such as bone morphogenetic proteins, BMP-2 and BMP-9) are considered the most potent biomolecules, and the delivery of BMPs into bone defect sites is a promising method to support bone regeneration. Therefore, a series of methods have been employed to develop BMPs replacement therapy, including growth factor therapy, gene therapy, and RNA therapy.
Table 1. Comparison of protein-, gene- and RNA-therapy.
| Growth factor therapy | Gene therapy | RNA therapy | |
| Mode of action | Binding to receptor to elicit signaling pathway | Endogenous transcription and translation into target protein | Modulation of endogenous protein expression |
| Location of action | Plasma membrane | Nucleus | Cytosol |
| Delivery vector | None | Viral or non-viral methods | Non-viral methods |
| Effect onset and duration | Fast and transient | Slow and long-term | Fast and transient, controllable kinetics |
| Advantages | No vectors needed, well studied | Long lasting effect, endogenous protein expression, not limited to growth factor expression (e.g. receptors) | Transient effect, endogenous protein expression, not limited to growth factor expression (e.g. receptors), good control of dose |
| Disadvantages | Fast degradation, loss of bioactivity, high production costs, risk of overstimulation | Risk of random genomic integration and carcinogenesis, non-viral vectors show low efficacy, risk of unwanted immune response | Fast degradation and low transfection efficacy without complexation, risk of unwanted immune response |
*Andrée, L., et al. 2021 (Materials Today Bio)
mRNA-based therapy for osteogenesis
Since the progress of understanding the bone remodeling mechanisms and the fast development of mRNA-based technology, mRNA has received increased attention as a novel tool for bone tissue engineering because of its unique feature and great potential to cure bone defects. Researchers have successfully demonstrated the safety and efficacy of using modified mRNA coding BMP-2 (one of the dominant osteoinductive factors) for bone regeneration in vitro and in vivo. The studies involved bone marrow-derived stem cells (BMSCs) and adipo-derived mesenchymal stem cells (AMSCs). For in vivo osteogenesis, the modified BMP2 mRNA presented high bone tissue repairability. In addition, besides BMP-2, BMP-9, another osteogenic factor, is highlighted to be used to support bone regeneration. A study had compared the efficiency of modified mRNA coding BMP-2 or BMP-9 in the aspect of in vitro osteogenic induction as well as in vivo bone regeneration. The results showed that they lead a similar ratio of bone volume to tissue volume, and modified BMP-9 groups had 2-fold more density in connective tissue than BMP-2 groups.
Schematic diagram illustrates the clinical feasibility of combining biomaterials with modRNA-treated BMSCs for bone repair. (Geng, Y., et al., 2021)
Applying mRNA for bone regeneration benefits from continuous efforts in mRNA structure optimization and purification strategies. Creative Biogene is a leading service provider for mRNA-based drug research and development. Our extensive experience, an excellent team of experts, and advanced technology platforms make us an ideal partner for worldwide customers. We can support our customers with the most affordable, high-quality custom mRNAs according to the desired applications. If you are interested in our services, please don't hesitate to contact us. We look forward to providing services for your next project.
References
- Andrée, L., et al. (2021). "Designing biomaterials for the delivery of RNA therapeutics to stimulate bone healing." Materials Today Bio, 100105.
- Geng, Y., et al. (2021). "BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways." Communications Biology, 4(1), 1-14.
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