Aibo Biotech's financing exceeds 700 million U.S. dollars!

In the COVID-19 pandemic, mRNA technology has brought huge imagination to the world
.

Compared with traditional vaccines, mRNA vaccines are fast, low-cost, and scalable

Just today, Abbbio announced the completion of Series C financing totaling more than US$700 million, setting another record high in the field of RNA therapy
.

The reason why mRNA vaccines can be sought after in the new crown epidemic is actually inseparable from another "behind-the-scenes hero"-LNP delivery technology

Why do you need a delivery system?

Why do you need a delivery system?

In 1993, scientists injected liposome-coated mRNA encoding influenza virus protein into the muscles of mice for the first time, evoking T cells that can recognize the protein, and firing the first shot of an mRNA vaccine
.

As the huge imagination space is opened up, a fatal problem is also posed before scientists-the protein sequence information encoded by mRNA must be sent to the cell to play a role in the ribosome

The body has a strict reconnaissance system that can identify foreign RNA and prevent them from being translated into proteins
.

In addition, the structure of RNA itself is unstable and highly sensitive to enzymatic degradation, and it is easily degraded by a variety of enzymes

Therefore, similar to other nucleic acid drugs, delivery problems must be solved in order to realize the wide application of mRNA
.

"Behind the scenes hero" LNP technology

"Behind the scenes hero" LNP technology

The two mRNA vaccines marketed in this epidemic both use Lipid nanoparticle (LNP) technology
.

LNP loaded with mRNA mainly includes four parts: ionizable lipids, PEGylated lipids, neutral auxiliary phospholipids and cholesterol

The structure of LNP-mRNA vaccine (Source: Vaccines)

The polarity of the lipid molecule changes with changes in pH
.

It carries a positive charge at low pH and can form a complex with negatively charged mRNA; under a neutral physiological state, the lipid molecule does not ionize, which can reduce toxic and side effects

LNP-mRNA vaccine and the process of entering the body (Source: Nature Reviews Materials)

LNP technology has been highly sought after since its inception
.

Patisiran (trade name: ONPATTRO®), the world's first RNAi therapeutic drug approved in 2018, uses this technology

Global mRNA vaccine delivery technology landscape

Global mRNA vaccine delivery technology landscape

Currently commonly used delivery technologies for mRNA vaccines include electroporation (Electroporation, Ep), lipoplexes (Lipolexes, LPX), protamine, cationic lipid complexes (lipoplex, LPX), and dendritic cells (dendritic cells).
cell, DC) and LNP mentioned above
.

Ep is also called electrotransfection, and its development is relatively mature
.

Ep can instantaneously increase the permeability of the cell membrane through the action of a high-strength electric field, allowing foreign substances to enter the cell

According to incomplete statistics from the NextPharma database and publicly available data, more than 30 of the more than 40 mRNA vaccine projects that have entered the clinic globally use LNP technology
.
It can be seen that LNP is the current mainstream delivery system
.

Source: Medical Rubik's Cube NextPharma and the compilation of public information

Domestic delivery technology layout

Domestic delivery technology layout

Before the Covid-19 epidemic, LNP technology had been developed for decades
.
It can be seen from the figure that China’s share of the number of LNP patents has risen sharply, exceeding 10% in 2020
.

The number and proportion of LNP related patents worldwide and Top 5 countries (Source: ACS Nano)

According to the NextPharma database of Medicine Cube NextPharma, domestic companies that deploy mRNA technology include Fosun Pharma, Aibo Biology, Watson Biology, Livanda Biology, Si Microbiology, Bendao Gene, Shenxin Biology, Jiachen Xihai, Blue Magpie Biology, Miele John Hancock, nanometer thick deposit, crown Hao biology
.
Only a few companies have independent intellectual property rights in delivery technology
.

The latest financing situation of some domestic mRNA technology companies with independent intellectual property rights in delivery technology (Source: PharmaInvest)

Note: The original text has been deleted

Reference materials:

Reference materials:

[1] Michael D.
Buschmann et al.
Nanomaterial Delivery Systems for mRNAVaccines.
Vaccines.
(2021).

[1] Michael D.
Buschmann et al.
Nanomaterial Delivery Systems for mRNAVaccines.
Vaccines.
(2021).

[2] Xucheng Hou et al.
Lipid nanoparticles for mRNA delivery.
NatureReviews Materials.
(2021).

[2] Xucheng Hou et al.
Lipid nanoparticles for mRNA delivery.
NatureReviews Materials.
(2021).

[3] Lipid Nanoparticles From Liposomes to mRNA Vaccine Delivery, aLandscape of Research Diversity and Advancement.
ACS Nano.
(2021).

[3] Lipid Nanoparticles From Liposomes to mRNA Vaccine Delivery, aLandscape of Research Diversity and Advancement.
ACS Nano.
(2021).