mRNA-Based Cellular Engineering and Reprogramming
Since genetic or acquired disorders can cause insufficient or defective protein synthesis, thereby leading to severe disease and even death. Reprogramming and transdifferentiation of cells using synthetic mRNAs to produce the desired proteins in cells is a very promising technique that makes possible the clinical application of these engineered cells. The improvements in mRNA synthesis and stability have promoted its use for de novo protein expression in cells. The target proteins can be produced in different cells by exogenous delivery of in vitro-transcribed (IVT) mRNA in a non-integration and transient manner. At present, the use of IVT mRNA combined with a series of approaches has been applied to control the expression profiles of cells by the production of proteins. IVT mRNAs encoding transcription factors have been utilized for several aspects of cellular engineering and reprogramming, including the efficient induction of pluripotency in somatic cells, generation of induced pluripotent stem cells (iPSCs), direct induction of the differentiation into the desired cell type, and so on. Creative Biogene is a forward-looking research institute as well as a leading custom service provider in mRNA research. We have extensive experience offering cellular engineering and reprogramming services based on IVT mRNA, especially in mRNA-based iPSC production, mRNA-based MSC engineering, and T cell engineering.
Application of mRNAs in cell and tissue engineering. (Badieyan, Z. S., & Evans, T. 2019)
Service offering in Creative Biogene
In recent years, the great potential of iPSCs in studying disease phenotypes and developing new drugs for therapy has attracted increasing attention. mRNA reprogramming technology has been emerging as a fast, safe, and efficient method that generates clinical-grade iPSCs from somatic tissue. We have put much effort into the optimization of mRNA-based reprogramming protocols in terms of various parameters, such as the numbers of transfections, different modifications of mRNAs, multiple vectors, and routes, as well as cell culture conditions. And finally, we have established a relatively simple process and an optimal protocol.
Mesenchymal stem cells (MSCs) emerge as a very attractive cell type for regenerative medicine due to their availability as well as their harvesting without ethical problems. Engineering of MSCs using mRNA has been proposed as a temporary and burst approach to regulating the migratory properties of MSCs through homing proteins. Our service has a strong capability to provide comprehensive technical support that includes the design of engineered MSCs, MSC engineering using mRNA transfection (with non-viral technologies), and evaluation of the engineered stem cells' functions in vitro and in vivo.
Direct transdifferentiation as an alternative approach to iPSC-mediated differentiation, enables the conversion of adult somatic cells to other types of cells without undergoing an intermediate state of stem cells (iPSC generation). Based on experienced experts and the latest advanced technologies, we are now proud to offer somatic cell transdifferentiation services using synthetic mRNA. According to different cell types and specific transcription factors, we can achieve the conversion of adult human fibroblasts into several lineages, including neural precursor cells, cardiomyocytes, and insulin-secreting cells, but not limited to them.
Adoptive T cell therapy is a promising form of cellular therapy. Adoptive T cell transfer generally requires ex vivo modification of isolated autologous cells. Therefore, a number of compounds and techniques for T cell engineering have been developed and evaluated, including in vitro-transcribed (IVT) mRNA. Generally, the use of mRNA transfection for T cell engineering includes isolation and expanding T cells, transfection of IVT mRNA, and cell quality control. Based on experienced experts and advanced instruments, we not only optimize T cell isolation and expansion methods but also offer electroporation of mRNA and LNPs-mediated mRNA delivery to facilitate the successful GMP-compliant production of T cells.
Macrophages, important cells of innate immunity, are known for their phagocytic activity and capability for antigen presentation and so on. Following FDA approval of CAR-T cell therapies, the development of therapeutic strategies characterized by reprogramming or modification of macrophages appears to be the next step in cellular immunotherapy. Here, we highlight cell therapy with mRNA-based modified macrophages as a rapidly developing field.
Features of our services
- Professional technical support.
- Optimization & scale-up platforms.
- Ready to start your project once the contract is signed.
- Fast and traceable testing for urgent project needs.
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- Steinle, H., et al. (2017). "Concise review: application of in vitro transcribed messenger RNA for cellular engineering and reprogramming: progress and challenges." Stem Cells, 35(1), 68-79.
- Badieyan, Z. S., & Evans, T. (2019). "Concise review: application of chemically modified mRNA in cell fate conversion and tissue engineering." Stem cells translational medicine, 8(8), 833-843.