CHEMICALLY MODIFIED mRNA: DELIVERY, CELLULAR INTERNALIZATION, AND ROLE IN BONE REGENERATION

Chemically modified mRNA (cmRNA) has emerged as a promising tool in regenerative medicine due to its ability to encode therapeutic proteins that stimulate tissue regeneration. This keynote lecture explores the advances in mRNA delivery systems, focusing on the strategies that improve cellular internalization and the stability of mRNA within the body. Emphasizing recent developments in lipid nanoparticle (LNP)-based delivery platforms and other novel vectors, the talk will address key challenges in achieving efficient and targeted delivery to bone tissues. Additionally, the potential of loading the cmRNA-LNP complexes into 3D biomaterials to obtain transcript-activated matrices will be highlighted. These matrices offer exciting possibilities for controlled release and enhanced tissue regeneration. Several examples will be presented to demonstrate the potential of this approach in promoting tissue healing and regeneration. Examples of cmRNA internalization into various cellular systems, such as fibroblasts, osteoblasts, stem cells, and neural cells, will be discussed to highlight the versatility and specificity of these delivery systems. Furthermore, the potential of cmRNA to support the differentiation of these cells into osteogenic, angiogenic, and neurogenic pathways will be examined, providing insight into the regenerative capacity of cmRNA-based therapies. Lastly, the role of cmRNA in promoting bone regeneration will be explored, including its potential to induce osteogenesis and accelerate healing processes in bone fractures and defects. Finally, the future of cmRNA technology in bone regeneration will be considered, with a focus on overcoming current limitations and the promising clinical applications on the horizon.