Regenerative Medicine and Cell Engineering
With the development of in vitro transcribed (IVT) synthetic mRNA, mRNA holds significant potential in the field of gene therapy. In contrast to conventional methods for the expression of target proteins, mRNA has numerous advantages, such as simpler process for protein expression in vivo, efficient expression of transcription factors, low risk of insertion mutagenesis and so on. These advantages make in vitro-transcribed (IVT) mRNA a powerful and promising alternative gene expression system for a wide range of applications in regenerative medicine, including reprogramming and transdifferentiation of somatic cells as well as mesenchymal stem cells (MSCs) engineering.
Regenerative medicine aims to replenish the damaged cells or tissues by restoring or establishing their normal physiological state. Numerous methods around the important roles of proteins as signaling molecules in the regeneration process have been investigated to accomplish this goal, such as cell therapy as well as tissue engineering approaches. To enhance the regeneration of injured cell or tissue, the delivery of functional proteins (e.g., growth factors and transcription factors) to a defect site is an available option. However, this strategy faces several problems due to the protein's low in vivo stability. mRNA-based therapy is an attractive alternative to conventional approaches because of the target proteins that can be generated via the cell translation machinery when the mRNAs are internalized by cells.
The applications of mRNA-based therapy in regenerative medicine
The first report of IVT mRNA mediating in vitro reprogramming of somatic cells was in 2010. The method is based on the generation of human induced pluripotent stem cells (iPSCs) from adult somatic cells by transfection with the IVT mRNA encoding transcriptional factors. It is a safe strategy for reprogramming cells to pluripotency, having the characteristics of efficiency and leaving no residual traces of transgenes. However, the induction of iPSCs is quite laborious. As an attractive alternative approach, direct cell reprogramming, also called transdifferentiation, allows adult somatic cells to directly transform to other cell types without the need to transition through an intermediate state of stem cells. The approach has been utilized in the generation of cardiomyocytes and insulin secreting cells.
MSCs are adult stem cells that have the migration, self-renewal capacity as well as the ability to differentiate into a wide range of cell lines, including cartilage, bone, and adipocytes. Moreover, MSCs can secrete various proteins, which take part in biological processes, such as reducing inflammation and angiogenesis. Since the engineering of MSCs with IVT mRNA allows to express homing proteins in a brief, burst, and temporary way, it is a potential alternative over other strategies of cell surface modification, avoiding permanent changes and the following disorders of the differentiation properties.
Fig1. Developmental plasticity. ESC, embryonic stem cell; iPSC, induced pluripotent stem cell. (Brumbaugh, J., et al. 2019)
Creative Biogene is your professional and reliable partner. We are committed to providing our customers with the finest services in the field of mRNA therapy. Based on the available state-of-the-art facilities and highly experienced staff, we are now offering a series of customized services, but not limited to them, including,
- mRNA design service
- Customized mRNA synthesis service
- A series of mRNA optimization services
- mRNA delivery vector service
If you would like more information about our services, please don't hesitate to contact us.
- Kwon, H., et al. (2018). "Emergence of synthetic mRNA: In vitro synthesis of mRNA and its applications in regenerative medicine." Biomaterials, 156, 172-193.
- Grath, A., Dai, G. (2019). "Direct cell reprogramming for tissue engineering and regenerative medicine." J Biol Eng 13, 14.
- Brumbaugh, J., et al. (2019). "Reprogramming: identifying the mechanisms that safeguard cell identity." Development, 146(23).