Drugdu.com expert's response:

The development of mRNA (messenger RNA) drugs has undergone a journey from early exploration to technological breakthroughs, and then to widespread application. The specific progression is as follows:

I. Early Exploration (1961-1990)

In 1961, scientists first discovered mRNA.

In 1987, Malone found that mRNA molecules mixed with lipid droplets could enter cells and express the desired protein, marking the beginning of RNA research as a therapeutic agent.

In 1990, scientists injected in vitro-transcribed messenger RNA (mRNA) into mice and discovered that it could be expressed in vivo, producing relevant proteins in a dose-dependent manner. This method of directly injecting mRNA could induce an immune response by expressing specific proteins, serving as the prototype for mRNA therapy.

II. Technological Breakthroughs (Early 21st Century-2020)

Entering the 21st century, mRNA synthesis, modification, and delivery technologies further advanced.

In 2005, Karikó and Weissman discovered that using modified nucleotides like pseudouridine could reduce the immunogenicity of mRNA, laying the foundation for mRNA vaccine development.

In 2015, researchers in Weissman's team discovered the significant clinical potential of lipid nanoparticles (LNPs). By constructing mRNA-LNP complexes, mRNA could be effectively delivered into cells.

III. Widespread Application (2020-Present)

During the COVID-19 pandemic in 2020, mRNA vaccines were approved by the FDA. With advantages such as high safety, strong immune response, low research and development costs, and rapid development speed, mRNA as a therapeutic molecule became a hot area in biomedical research.

In 2021, Pfizer's BNT162b2 vaccine and Moderna's mRNA-1273 vaccine generated revenues of 40.4billionand17.675 billion respectively, becoming the top and third-highest-selling drugs globally.

It is projected that the therapeutic mRNA market will reach 20.83billionby2025and42.64 billion by 2034.

IV. Mechanism of Action of mRNA Drugs

The mechanism of action of mRNA drugs is primarily based on the characteristic of mRNA directing protein synthesis. The specific process is as follows:

Vaccine Construction: mRNA drugs contain a synthetic mRNA molecule that includes partial genetic information of a pathogen (e.g., a virus), typically related to viral surface proteins. These proteins are the targets for the immune system to recognize and produce antibodies against.

Injection into Cells: mRNA drugs are injected into the recipient's cells. In the case of COVID-19 mRNA vaccines, this is often done by injecting into muscle cells.

Translation to Produce Antigen Proteins: The mRNA fragments in mRNA vaccines encode certain proteins or receptors on the surface of the coronavirus, such as the spike protein (S protein). The vaccine delivers artificially edited mRNA into human cells, which then "borrows" the recipient's own cells to translate the mRNA into proteins. After translation, this mRNA expresses an antigen protein characteristic of the virus.

Induction of Specific Immune Response: Although the antigens produced are manufactured by the body's own cells, due to the exogenous nature of their amino acid sequences, toll-like receptors (TLRs) in antigen-presenting cells (APCs) do not recognize this sequence. Consequently, it still stimulates a specific immune response from B cells and T cells against this antigen protein and establishes immunological memory.