Catch up while advancing, is there any shortcut for China's mRNA industry?

Looking back over the past 10 years, mRNA technology has developed very rapidly.
Moderna has a market value of 90 billion US dollars (as of the date of publication, it has exceeded 160 billion US dollars in market value)
.

BioNTech, ranked second, also has a market value of US$50 billion (as of press date, it has a market value of more than US$90 billion)
.

Although CureVac ranks third in market value, it is still strong, with a market value of more than US$10 billion
.

From a development perspective, mRNA companies need to have complete commercialization capabilities, including but not limited to product development, production, sales and other links.
They mainly face five problems and challenges:

01 mRNA core competence-delivery system

The delivery system refers to encapsulating the mRNA in a lipid carrier, suspending the lipid in an ethanol solution, contacting the mRNA and encapsulating it, the two substances are attracted by opposite charges, and the original solution is filtered through tangential flow filtration (TFF) to remove the solution.
The excess lipids, alcohol and other impurities are removed, and the final mRNA vaccine solution is made
.

The delivery system of mRNA is demanding, and the "cargo" that needs to be carried is 600-10.
000 kDa.
At the same time, because mRNA has a complex secondary structure, its expanded spatial rotating sphere is large, which makes delivery difficult; for this reason, even at present The head company BioNTech also had to change its original delivery system (LPX) to LNP, and Moderna directly used the LNP delivery system that belongs to Arbutus, at the risk of being sued for the first time
.

In addition to the above-mentioned problems that can be directly solved by the delivery system, other potential problems include: non-specific cellular uptake, off-target effects (siRNA), insufficient activity or even lack of activity (mRNA)
.

The delivery system is one of the biggest bottlenecks in the production of mRNA vaccines .
One of the important reasons is that the number of manufacturers that provide lipids on the market is limited.
Even if the lipid carrier is independently developed, the patents and other issues involved still cloud the scale-up production at this stage.
A layer of shadow
.

Lipid carrier systems are very scarce resources in the mRNA industry and even the world.
If a new delivery system is discovered and verified in animals, the global value of this delivery system is extremely high
.

The delivery system of Microbes is an LPP delivery system in cooperation with Professor Shen Haifa, a professor of the Department of Nanomedicine at Cornell University Houston Methodist Hospital, which avoids the structure patent of LNP
.

02 mRNA sequence optimization algorithm

Large companies like Moderna usually choose to cooperate with cloud computing platforms (Amazon, etc.
) to solve the problem of sequence optimization
.

Si Microbial Selection has cooperated with top domestic AI companies for two years and developed a unique algorithm to calculate the sequence of codons with the help of "AI + cloud computing" technology
.

Compared with the traditional sequence optimization platform, S.
Microbial can increase the expression efficiency by 3-4 times and reduce the mRNA degradation ratio
.

03 Preparation Technology

The research of the CMC part usually requires formulating, particle size, potential, route of administration and other influencing factors to screen LPP delivery systems targeting different tissues and organs
.

Screening the lipid structure in the delivery system is also a great challenge.
Moderna has screened hundreds of lipid structures.
At present, Sri Lanka has screened nearly a hundred lipid structure combinations.
The screening process is complicated and time-consuming and labor-intensive
.

Preparation technology is one of the challenges faced by mRNA.
It is necessary to constantly try to break through the corresponding technology, so as to achieve the conventional cold chain and meet the transportation conditions of 2-8 degrees
.

The following table lists the comparison of the stability data of S.
Microbiology's products and vaccines on the global market
.

Superfluid control technology also has certain limitations in the field of vaccines, and the flow rate is limited; Si Microbiology has spent nearly three years, and a company in Suzhou has invested more than 10 million yuan to jointly develop a machine designed according to a flow rate of one liter per minute
.

04Supply Chain

To achieve large-scale production of mRNA vaccines, the supply chain will be a challenge
.
This includes key raw materials, materials, supplies, equipment and so on
.

Based on the entire supply chain, mRNA may encounter problems in the entire technical route, such as the management and regulation of raw material supplier Thermo Fisher Scientific and domestic dragon head Zhaowei, and even the selection of phospholipids are challenging
.

The barrel theory is suitable for mRNA companies, and the shortcomings of any link will limit the scale of mass production
.

05Product pipeline

Comparing domestic companies with the world's leading companies, the product pipeline is still not rich enough
.

Compared with Moderna's infectious disease and tumor pipelines, many of their products have entered the first and second phases.
Even as a Chinese head mRNA company, only one vaccine has entered the clinical stage.
Compared with the world's top mRNA companies, There is still a big gap
.
Moderna also has a wealth of products in the pipeline of rare diseases and gene editing
.
In order to catch up with the world's leading companies, Si Microbiology established a branch in the United States to focus on the antibody business
.