Nucleic acid medicine is one of the frontier fields with the most clinical potential in the future biopharmaceutical industry. Frost & Sullivan (hereinafter referred to as "Sullivan") officially released the Research Report on the current situation and future development of nucleic acid medicine market industry (hereinafter referred to as "the report") on May 20, 2022 to sort out the development process of nucleic acid medicine industry, focus on the key R & D technology of nucleic acid medicine and gain insight into the future development trend of the industry, It provides a reference for those concerned in the field of nucleic acid drugs.
In the historical process of fighting diseases, traditional drugs take "protein" as the drug target. However, many "pathogenic proteins" are not drug targets in the human body , so many diseases lack effective treatment. In order to solve this problem, people have developed nucleic acid drugs along the central law and using the translation or regulation function of nucleic acid molecules to solve the unmet clinical needs caused by "non drug" targets. It is expected to become the third main drug after small molecule and antibody drugs. In recent years, many kinds of heavy nucleic acid drugs have come out successively, showing unprecedented application value in the treatment of metabolic diseases and the prevention of infectious diseases. The report deeply analyzes mRNA to explore the opportunities and challenges faced by nucleic acid drugs.
According to the use and type of drugs, mRNA drugs have three main application directions, including infectious diseases vaccine (preventive vaccine), tumor therapy (therapeutic vaccine) and protein replacement therapy (therapeutic drugs).
At present, mRNA technology is prominent in the application of preventive vaccines. It has fast development speed and obvious advantages in dealing with sudden epidemiological crisis. At the same time, the production capacity climbs very fast, and the batch output can reach 100 million doses. Compared with traditional vaccines, mRNA vaccines have excellent immune activation ability. Through endogenous expression of antigen proteins, they can induce more extensive and effective cellular and humoral immune responses and produce higher protection rate. Hundreds of millions of doses of mRNA coronavirus vaccine have verified the safety and efficacy of mRNA technology. MRNA technology has obvious advantages and will become an important choice for the development of new vaccines.
Due to the huge molecular weight, strong immunogenicity and easy degradation of mRNA, there are many obstacles in the development of mRNA drugs. In order to solve these problems, the mRNA structure, delivery system and production technology can be optimized.
The main delivery carrier technologies of mRNA drugs include liposome nanoparticles, protamine carrier, polymer carrier and so on. At present, liposome nanoparticles are the most widely used delivery system. When the pH of the lipid carrier complex is positive, the interaction between the lipid carrier and the nanoparticle in the blood can be reduced, which can increase the stability of the membrane. After being ingested by cells, the acidic environment of endosomes makes them carry positive charge again, which may help to destroy the stability of endosomal cell membrane and promote the detachment of mRNA from endosomes. LNP also carries other lipid molecules, including phospholipids, cholesterol and polyethylene glycol (PEG), which can help improve the stability, delivery efficiency, tolerance and biological distribution of LNP. The defect of ionizable LNP is that it will still lead to the release of inflammatory cytokines, lack of targeting ability and poor stability of liposomes. Improving the safety and stability of LNP is the key to future research.
MRNA vaccine is a general platform technology, which provides a flexible, rapid, large-scale and cost-effective production process. It has obvious advantages in the face of the threat of new coronavirus pandemic. At the same time, according to the phase III clinical results, the mRNA neocoronal vaccine showed better protective efficacy and immune system activation ability than other neocoronal vaccines.
2020 is a breakthrough year for mRNA vaccine. Two new mRNA coronal vaccines developed by Pfizer / biontech and Moderna have been authorized for emergency use. In 2021, the global sales revenue of the two mRNA coronavirus vaccines reached US $58.7 billion, far exceeding that of other coronavirus vaccines.
In the short term, the main contributor to the future market of mRNA products will still be the new crown vaccine. In addition to Xinguan, in the field of preventive vaccines, the main market opportunity lies in the unmet immune needs, such as the development of Zika, HIV, EBV, RSV and other viruses.
In the field of tumor therapy, mRNA is designed and produced rapidly, and has certain advantages in personalized tumor vaccine. Both biontech and Moderna have entered the clinical stage, but the application of tumor vaccine is still in the stage of conceptual verification; In the field of protein replacement therapy, there are still key technical bottlenecks. In the future, we need to overcome the two obstacles of poor targeting and unstable expression.
Source:Pharnex
