MrRNA under the wind, a big bet or the next Nobel Prize?

A new crown vaccine research and development competition, so that mRNA technology once again stand in front of the historical stage.
a "big gamble" on the mRNA vaccine, just behind the recent news that Watson's bio-phone would blow up the medical world.
After the conference call, on the 7th, Zhifei Bio announced that it intends to subscribe for a 10.189 percent stake in Convinced Bio with its own funds of 35 million yuan, layout of the third generation of mRNA vaccine technology platform.
, mRNA technology has become the brightest star on stage in this year's new crown outbreak.
experts say mRNA technology is on track to win the next Nobel Prize.
the technology was not widely used until the British government approved the emergency use of Pfizer and BioNTech's new crown vaccine.
recent years, RNA therapy has been one of the hot topics in gene therapy.
, RNAi technology and mRNA technology are the two dominant areas of RNA therapy.
But compared to RNAi, which has the potential to synthesize "any protein" that transforms protein-making engines in cells into "drug factories," the mRNA technology has failed to stir up water.
since the completion of the proof-of-concept in the 1990s, how to solve the problem of mRNA stability and delivery has long constrained the development of this field.
, however, as technology advances, investor enthusiasm is growing.
the pool is already packed with competitors, even though no products have yet been born.
the 21st century, CureVac AG, BioNTech and Moderna, now the big three in the mRNA field, were founded and are showing a three-legged trend.
three companies already account for the vast majority of all research and development pipelines in mRNA therapy.
companies and research institutions in the pool are also trying to develop their own products and try to get a piece of the pie.
currently, mRNA technology has two main applications: infectious diseases and cancer.
now appear to be at the forefront of the development of infectious disease vaccines.
with the first new mRNA vaccine in the UK, many in the industry believe a critical time has come to test the success or failure of the technology.
the new crown vaccine, mRNA will also redefine vaccine development techniques.
To make the "in vivo factory" work, researchers have battled mRNA's two major challenges since the 1950s, when Crick proposed the central law of DNA, RNA to proteins, and scientists have dreamed of being able to treat or prevent disease by injecting specific mRNAs (messenger RNA) to guide human cells to quantify a protein.
, mRNA is "worker" if human cells are treated as an "in vivo factory".
find the right "worker" to allow the "factory" to produce the "drugs" it needs to treat its own diseases - specific proteins.
means that if humans can control mRNA, they will be able to create the ideal therapy as they please.
, it's not easy to turn this wonderful idea into reality.
and American bioscient scientist Katalin Kariko is a key figure on the road.
1978, Kariko began studying mRNA.
was subject to the level of biotechnology at the time, mRNA application technology hit the iron plate, and she was dismissed by Hungarian research units for scientific research.
time, because mRNA causes the body's immune system to overreact, thus risking humans, leading to the field in the academic community is almost "a pool of stagnance."
difficulties in research and development, Kariko also moved to the United States.
, the direction of mRNA treatment in the United States was still on the rise.
1998, Kariko, already a professor at the University of Pennsylvania, met drew Weissman, an immunologist, and the two began working together on mRNA.
2005, half a century had passed since the central law.
this time, the application of mRNA technology finally ushered in a new breakthrough in Kariko and Weissman's research.
they found that by slightly adjusting the nucleoside structure of mRNA, it could be kept low-key, avoiding the immune system's monitoring of new mRNA and initial immune response.
the heavy discovery didn't make much of a splash at the time, it caught the attention of two characters.
, the two men founded Moderna and BioNTech, two giants in the mRNA field.
, Moderna has focused on new nucleotide modification technologies and has been operating in "stealth mode" for years.
the end of 2012, Moderna had filed more than 80 patent applications for mRNA technology, involving more than 4,000 claims, including chemical modification, RNA engineering, formulation, substance composition, route management and administration.
same time, Moderna, who has been "in the dowl" for many years, has emerged as a preclinical program in four areas: cancer, genetic diseases, haemophilia and diabetes.
almost the same time, BioNTech began a similar journey.
hired Kariko as senior vice president to oversee the manufacture of specific mRNAs.
on the shoulders of Kariko and Weissman's findings, mRNA technology still has two key factors in achieving disease treatment.
Because exogenous mRNAs must penetrate the lipid membrane barrier to enter the cytoste and be successfully translated into the desired protein, for delivery problems, it is necessary to ensure that the types of cells that can be delivered are sufficient and that appropriate preparations are needed to protect mRNA from the degradation of extracellular RNase mediatation and promote its entry into cells.
this problem, but also determines the enterprise's drug pipeline and development rhythm.
addition, in addition to delivery problems, but also to avoid immunogenicity, control mRNA protein translation efficiency.
Modelna, for example, initially used liposome technology to deliver, but this led directly to the failure of the early product line by activating a strong inflammatory response and hepatotoxicity.
in subsequent product development, Moderna claimed to have used its own new lipid delivery technology, but this also raised questions from another company, Arbutus, and filed a lawsuit against Moderna for illegally using its LNP delivery technology.
controversy is not just about delivery technology, but Moderna's nucleoside modification technology is also mired in patent disputes.
, but in recent years, with the rapid development of this field, there have been many new solutions around these two issues.
, the big three, Modelna, CureVac and BioNTech, all use lipid nanotechnology delivery (LNP), which is currently the most widely used delivery technology in the field of nucleic acid drugs.
technology around proteins, each is also working to achieve breakthroughs differently.
CureVac owns the RNArt technology platform.
RNArt is RNA that encodes proteins and can supplement or replace proteins in the original cell.
currently has a treatment program for shallow tumors in the preclinical research phase.
And in 2019, Moderna announced a major technological breakthrough, with the company's mRNA-1944 therapy, which encodes chikungi virus antibodies, showing good safety and antiviral activity in Phase I clinical trials, the first systemic mRNA therapy to encode secretion proteins, using the lipid nanoparticle (LNP) delivery technology developed by Moderna.
gene therapy outside the insertion of tumor immunity, open up market prospects In recent years, with the stability of mRNA synthetic modification technology and delivery technology breakthroughs, mRNA in the traditional vaccine is ineffective for a variety of new viruses, cancers, metabolic diseases and other broad application prospects.
, director of New York at Good Health Capital, said: "mRNA is really a platform on which more personalized treatments can be achieved.
" in comparison with traditional vaccines and DNA vaccines, mRNA vaccines have the advantages of short research and development cycle, relatively low research and development costs, high safety, better water solubility, strong design and rapid preparation, which brings great imagination space to the market.
The global market for mRNA preventive and therapeutic vaccines is expected to grow at a compound annual rate of 32.0 percent between 2020 and 2025, up from $1.97 billion in 2019 to $5.98 billion by 2025, according to Market Research Report LLC.
, despite the difficulties and breakthroughs in research and development, the field has attracted the attention of many capital and pharmaceutical giants.
2018, Moderna set the record for the largest IPO of a U.S. biotech company in U.S. history without product output, with a total of more than $2 billion raised.
BioNTech also took nearly $700 million in pre-NASDAQ listings.
in the big three research and development cooperation, there is no shortage of AstraZeneta, Genente, vaccine giant Pfizer, Mercer East, GlaxoSmithKline and other pharmaceutical giants.
moshadon invested $100 million in Moderna in cash and stock as early as 2015, when the mRNA track was little known.
three years later, Mercedon's additional investment of $125 million shows its optimism about the track.
, the mRNA giant is pushing for gene therapy and cancer vaccines, even as the new crown outbreak disrupts the pace of research and development.
in recent years, as research competition for immuno-checkpoint inhibitors (ICIS) such as PD-1 has entered the white heat, giants have begun extensive trials of water tumor vaccines and ICIs such as PD-1. "The general cancer vaccine needs to be used in a coalition with ICIs such as PD-1 inhibitors because it provides an immune-activated tumor microencase,"
's founder, Li Lin-hsin, said in an interview with the media.
currently, the use of mRNA cancer vaccines with ICIs is a conventional strategy.
recent studies, researchers have found that new mutations in tumor cells that continue to appear during growth can lead to the emergence of a new antigen on the surface of tumor cells.
of this new antigen may be the cause of differences in immunotherapy outcomes.
, developed in collaboration with Moderna, is intended to find new antigens in tumor cells, and to maximize the effectiveness of immunotherapy by using Mercadon's PD-1 collaboration after mRNA kills cancer cells of new antigens.
publicly showing that the current collaboration between Mercadon and Moderna is primarily two research and development pipelines, the personalized tumor vaccine mRNA-4157 and the Kras tumor vaccine mRNA-5671.
, the personalized tumor vaccine mRNA-4157 has entered clinical phase II.
kras is a difficult target at the moment, and the vaccine is currently in clinical phase I.
, regeneratives are also working with BioNTech to use mRNA cancer vaccines and PD-1 in the treatment of melanoma.
In addition, in the current hot cell therapy field, due to the clinical TCR-T and CAR-T mainly use viral carrier system preparation, but the virus carrier system preparation process is complex, there are risks, there are currently some clinical trials are using mRNA instead of viral vector line tumor immunotherapy.
the international market mRNA, the domestic geometric international market has long been in the air, the domestic market from 2015 onwards, the main mRNA enterprises appear.
but until now, China's mRNA research and development companies are few and far between.
, Europe and the United States have established high intellectual property patent barriers and master key technologies in the field of mRNA, while lower maturity and higher risk of mRNA are important factors.
, after all, there are already three drugs on the market compared to RNAi technology in the same RNA therapy, and mRNA therapy has not been available for a long time.
, China's mRNA enterprises are mainly microorganisms, Abo Bio, Convinced Biology and Mano Hengkang and so on.
in Shanghai in 2016, the mRNA drug treatment area has two types of pipelines for infectious diseases and tumors.
, which was founded in 2019, focuses on technology such as mRNA vaccine development, molecular design, and delivery systems.
the same time, after this year's outbreak of the new crown vaccine, a number of domestic pharmaceutical companies, especially vaccine companies have also chosen to lay out the field through cooperation.
Fosun Pharma, in partnership with BioNTech, and Tibet Pharmaceuticals invested 351 million yuan in products such as the new microbial crown mRNA vaccine, and vaccine company Concino Bio, while developing the new crown vaccine for adenovirus vectors, also worked with Canadian company Precision Nano Systems to develop the new crown vaccine for mRNA.
just over the weekend, Watson Bio "sold" its upcoming vaccine products to "bet" on the mRNA vaccine to ignite the pharmaceutical industry.
May, Watson Bio and Abbott Bio signed the Technical Development Cooperation Agreement for the new coronavirus vaccine for mRNA, which will be used to conduct clinical research and commercial production of the new coronavirus mRNA vaccine.
the vaccine was approved for clinical trials in June and is currently in phase I clinical trials, according to Watson Bio's November announcement.
fact, until the new crown outbreak, the industry believed that there were safety issues compared to the short window period for mRNA drugs, and that the mRNA vaccine injected under the skin, especially personalized