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Unlocking the mRNA technology behind the promise of life-saving therapeutics

Human body contains trillions of cells, every one of which contains proteins to play a decisive role in multiple biological activities such as growth, development and mutation. There are over 100,000 different kinds of proteins performing different physiological functions. Incorrect production of proteins caused by genetic mutation will lead to cancer or other fatal diseases. Therefore, if we are able to rectify the incorrect mechanism in protein synthesis, human bodies will be transformed into a full developed biomedical factory to fight against diseases. Messenger ribonucleic acid (mRNA), synthesized from a DNA template, carries information from DNA to the ribosomes in the cell to deliver the right message of protein production. By cutting edge technologies, scientists are expected to develop any mRNA-based therapeutics and revolutionize the treatments for diseases that cannot be overcome by traditional therapies.

The tangled history of mRNA-based drug discovery

mRNA technology has been in development since the 1960s. but it has never been proven obviously responsive until COVID-19. For over half a century, three major challenges including the stability of mRNA, delivery efficiency and manufacturing have been hindering mRNA-based drug discovery. Nowadays, its success in combating the pandemic has resulted in renewed interest in development of other mRNA-based therapeutics. The history of mRNA development is both a marathon and a relay race. As we look back, all the milestones and breakthroughs of mRNA science and technology are jointly laying a solid foundation for this medical revolution.

The proprietary mRNA platform

Since the establishment and with years of pioneering mRNA research, our vision has always extended beyond therapeutic development. Leveraging on our leading platform, we will make mRNA-based drug discovery more efficient, effective and safer, which is vital to improving more lives. That is why we consider our proprietary mRNA technology platform our greatest innovation assets.

Abogen is one of very few mRNA biotech companies in the world which possess all key cutting-edge technologies in-house to support full cycle development and operation of mRNA-based therapeutics, ranging from target selection, sequence design, plasmid preparation, in vitro synthesis of mRNA, lipid molecule design, formulation, clinical research, GMP production, to the delivery of mRNA therapeutics to the market.

The platform serves as the engine driving our continuous exploration in mRNA research and development. We have developed mRNA vaccine product candidates for COVID-19. With further improvement of our platform capabilities, we will continue to extend our pipeline to prevention and treatment of other infectious disease, tumor immunity, protein replacement therapy, etc. to deliver the greatest possible impact to people through transformative therapies.

mRNA design, synthesis, and modification
Synthetic mRNA molecules are the active drug substances of mRNA therapeutics. These molecules carry genetic information and instruct human cell to synthesize necessary proteins that can help our body either fight infections or prevent diseases. The structure of mRNA molecule can be divided into five components, including the 5'cap, the 5' and 3' untranscriptional region (UTR), the open reading frame for the gene of interst, and the poly(A) tail. Each component is crucial to the stability and quality of the final product.
Our unique technology is capable of synthesizing high-purity mRNA with various optimization methodologies to encode functional proteins, so as to increase the translation efficiency and minimize the undesirable activation of the immune system. With the help of AI, computational biology, high-throughput screening, we have continuously improved the design and optimization of mRNA sequences, promoting the progress of more ideas in early discovery.
Our mRNA design and synthesis capabilities were validated by the advancement of our COVID-19 mRNA vaccines. It only takes a few weeks from sequence design to preclinical studies allowing us to track the evolving pandemic and adapt next-generation vaccines to new variants efficiently.
Lipid nano particle (LNP) delivery system
Efficient delivery requires that the mRNA be protected against extracellular degradation. We have accumulated extensive expertise on lipid nanoparticles (LNPs) as non-viral vectors for the delivery of mRNA to target cells. Our proprietary LNPs system can effectively protect the mRNA from degradation, deliver the mRNA to the desired tissues and facilitate the membrane transport, thus to achieve the efficient delivery of mRNA into cells. In addition to the novel cationic lipid used in the COVID-19 vaccine, we have built up a library of cationic lipids and will keep developing new compounds with better efficacy and/or lower toxicity. We also explore new formulations for developing pipelines.
Clinical & commercial manufacturing
mRNA-LNP is formulated with lipid ethanol solution and mRNA solution at appropriate flow rates and ratios. The encapsulation efficiency and polymer dispersion index (PDI) are the primary indicators for evaluating quality, which require precise control over such parameters as LNP components, particle size, flow rate, and fluid morphology at a high speed without compromising the quality.
We are one of the few companies with mass-scale capacity to manufacture lipid nanoparticles in accordance with rigorous standard. Our unique dynamic precision mixing (DPM) technology produces highly uniform, low-toxic, positively charged, and pH neutral lipid nanoparticles, achieves over 90% encapsulation rate, and allows linear amplification and mass-scale production, ensuring scalable, reliable and efficient supply of mRNA vaccines during pandemics.