mRNA-based Therapeutics Development
A number of rare diseases stem from dysfunctional or defective proteins. mRNA therapies have the capacity to treat rare diseases by regulating protein expression through the delivery of correct genetic information. There are still a number of issues that need to be solved before mRNA can work as a universal therapeutic modality for all mRNA based rare diseases. Our company is focused on creating new technologies, such as optimizing the mRNA sequence, increasing the timing and level of mRNA expression to aid our clients in overcoming the obstacles in mRNA therapy development.
Introduction to mRNA Therapy
The tremendous success of mRNA application in the COVID-19 vaccine proves the feasibility of developing the next generation of mRNA-based therapies. The delivery of mRNA to tissues restores protein function is much more effective than traditional methods. mRNA therapy increases the chances of correct mRNA dose formulation for each individual case unlike the viral vector mediated gene delivery approaches which alter genomic DNA.
Plans of establishing mRNA drugs are shown to be useful in infectious disease prevention and treating heart failures, along with several genetic disorders. There are clinical trials underway for paracrine vascular endothelial growth factor (VEGF) and CRISPR-Cas9 mRNA for heart failure, and some rare genetic disorders, respectively. Other fast-progressing mRNA drugs for rare diseases such as methylmalonic acidemia (MMA) and cystic fibrosis (CF) include mRNA-3704 and MRT-5005. While there’s still some trepidation towards mRNA therapy, the newfound technology is bringing us closer to solving previously unsolvable rare diseases that would be otherwise very difficult to treat.
Fig. 1 Potential therapeutics of rare genetic metabolic diseases with mRNAs. (Berraondo P, et al., 2019)
Our Services
We focus on helping researchers and executives design and implement a comprehensive strategy to create successful mRNA drugs for rare diseases. To achieve this goal, we offer a wide range of services that 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
To increase the therapeutic effectiveness of mRNA therapies, we offer multiple modification strategies which enhance the efficiency of protein expression. Our focus is on five key elements of mRNA: 5' cap, 5' UTR, ORF, 3' UTR, and PolyA tail. These modifications can aid in improving the translation and stability of mRNA, decreasing the immunogenicity of mRNA, and increasing the levels of expressed proteins. Other feasible strategies are also within our scope: - 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 can provide our clients with an enhanced mRNA packaging systems to improve the delivery of mRNA cargo such as:- Ionizable lipid nanoparticles (LNPs)
- Cell-based packaging
- Extracellular vesicle–based packaging
- Biomimetic packaging
- Targeting mRNA therapeutics to specific tissues
We assist our clients in constructing more refined in vivo delivery systems, especially for targeting solid organs such as the heart, kidneys, brain, and lungs to maximize the efficacy of mRNA therapeutics. For instance, the creation of catheter delivery systems and engineered packaging systems which bind to cells of specific tissues.
We pride ourselves in our remarkable accomplishments in molecular biology, genetics, RNA technology, and nanotechnology. Therefore, we are able to offer clients scientific services and technical support during the development of mRNA-based gene therapies for rare diseases. Our clients do not have to worry because we endeavor to help them improve the stability, immunogenicity, translation efficacy, and the delivery systems to enable the efficient and safe delivery of mRNA. If you are interested in our services, please contact us for more details.
Reference
- 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.