mRNA-based Therapeutics Development
Many rare diseases are caused by dysfunctional or defective proteins. By providing the correct genetic information, mRNA therapies can regulate protein expression to treat rare diseases. However, a number of challenges remain to be addressed before mRNA can be established as a universal therapeutic modality for rare diseases. Our company is committed to developing a range of new technologies, including optimizing mRNA sequences, increasing the timing and level of mRNA expression, improving mRNA delivery systems, and developing in vivo transdermal delivery systems to help our clients overcome the challenges in mRNA therapy development.
Introduction to mRNA Therapy
The remarkable success of the mRNA COVID-19 vaccine hints at the potential to develop the next generation of mRNA therapies beyond vaccines. Restoring protein function by delivering mRNA to tissues offers considerable advantages over conventional approaches. Unlike viral vector-mediated gene delivery methods, mRNA therapy corrects protein function without altering genomic DNA and allows the ideal dose to be formulated for each patient.
Drugs based on mRNA have significant application potential in the fields of infectious disease prevention and the treatment of various diseases. A series of clinical trials of mRNA therapeutics have been initiated, including studies of paracrine vascular endothelial growth factor (VEGF) mRNA for the treatment of heart failure and of CRISPR–Cas9 mRNA for the treatment of rare genetic diseases. In the field of rare disease therapeutics, fast-progressing mRNA drugs include mRNA-3704 for methylmalonic acidemia (MMA) and MRT-5005 for cystic fibrosis (CF). With the rapid development of mRNAs, intracellular vectors, and in vivo delivery systems, mRNA therapy brings new hope to many patients with rare diseases that cannot be easily satisfied by other treatments.
Fig. 1 Potential treatment of rare genetic metabolic diseases with mRNAs. (Berraondo P, et al., 2019)
We offer solutions for every stage of the mRNA therapy development workflow to help researchers and manufacturers develop and scale up mRNA therapies for rare diseases. Our services include, but are not limited to:
- mRNA synthesis for the development of therapeutics
We provide our clients with plasmid DNA (pDNA) preparation, mRNA in vitro transcription and capping, and purification and analysis of mRNA.
- Modifications of mRNA
We provide our clients with a variety of mRNA modification strategies to improve protein expression efficiency and thereby enhance the therapeutic efficacy of mRNA therapies. We focus on the optimization of five major structural domains of mRNA, including 5' cap, 5' end untranslated region (5' UTR), open reading frame (ORF), 3' UTR, and PolyA to enhance translation and stability of mRNA, reduce the immunogenicity of mRNA, and increase protein expression levels. We also offer other modification strategies:
- Chemical modification of nucleosides, which can significantly increase protein expression after transfection in vitro or in vivo.
- Codon optimization of mRNA sequences, which promises to develop effective therapeutic mRNAs without chemical modifications.
- Optimization of mRNA structure, which could improve the duration of its expression of proteins. Examples include self-amplified mRNA (saRNA) and circular mRNA (circRNA).
- Optimization of mRNA packaging systems
We offer our clients improved mRNA packaging systems to enhance the delivery of mRNA cargo, including:
- Ionizable lipid nanoparticles (LNPs)
- Cell-based packaging
- Extracellular vesicle–based packaging
- Biomimetic packaging
- Targeting mRNA therapeutics to specific tissues
We help our clients develop more advanced in vivo delivery systems, particularly for specific delivery to solid organs such as the heart, kidneys, brain, and lungs to realize the full potential of mRNA therapeutics. For example, the development of catheter delivery systems and engineered packaging systems to control tropism.
With our rapid achievements in molecular biology, genetics, RNA technology, and nanotechnology, we are well-positioned to provide scientific services and technical support to our clients throughout the development of mRNA-based gene therapies for rare diseases. We strive to help our clients improve stability, immunogenicity, translation efficiency, and delivery systems for the efficient and safe delivery of mRNA. If you are interested in our services, please contact us for more details.
- Berraondo, P.; et al. Messenger RNA therapy for rare genetic metabolic diseases. Gut, 2019, 68(7): 1323-1330.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.