How far is RNA therapy from us?

How far is RNA therapy from us?

39-year-old Carlos suffered from hereditary transthyretin amyloidosis (hATTR), a rare disease caused by the misfolding of the transthyretin protein, when he was approaching his innocent years.

At that time (2004), patients diagnosed with this disease survived only 15 years at most, and the only effective treatment was organ transplantation.

With the gradual approval of RNA therapy by the United States and the European Union in 2018, and the commercialization of RNA therapy technology, more and more patients are expected to be able to return to ordinary lives through RNA therapy like Carlos.

Post-it notes in "Life Restaurant"

Ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) can carry life information.

Also because RNA is unstable and easily degraded, RNA plays an important role in the execution of life functions.

One of the most important functions of RNA is to act as a messenger (mRNA) for gene expression.

Suppose you follow the fragrance and come to a restaurant to sit down and pick up the menu written by DNA.

If the mRNA content of the post-it note in the hands of the waiter is modified, even a small change will cause the protein to be synthesized incorrectly.

The disease that Carlos suffered was precisely because of genetic errors that caused the misfolding of transthyretin, which in turn triggered the production of toxic proteins and their accumulation in the organs, eventually leading to organ failure.

RNA therapy-save the "dark restaurant"

Many congenital genetic diseases are caused by the lack of key proteins or the presence of toxic proteins in the patient's body.

Compared with the DNA editing therapy that is still under development, stable, reversible and safer RNA therapy has become an important choice for the treatment of genetic diseases.

Wrong post-it notes can be modified or destroyed directly, so that the chef will not receive the wrong menu and will not make unpalatable dishes.

RNA can pair with RNA or single-stranded DNA antisense to form double-stranded molecules, forming double-stranded molecules that are difficult to read by ribosomes.

Alternatively, we can use small RNA molecules such as siRNA (small interfering RNA) or miRNA (microRNA) to prevent the translation of mRNA into protein.

We can also regulate proteins directly through RNA.

Of course, we can prevent the production of protein through RNA, and we can also produce the correct protein through mRNA.

If we deliver the characteristics of some pathogens, such as the spike protein mRNA of the new coronavirus, into the human body, some cells of the human body will also produce the characteristics of the new coronavirus and be recognized by the immune system, and finally form an immune memory.
Compared with the cumbersome production process of inactivated vaccines and the longer development cycle of recombinant vector vaccines, mRNA vaccines are also regarded as future vaccines because they are relatively simple to synthesize and can quickly, efficiently and flexibly adapt to the virus pandemic.

The development process of RNA therapy-flying from the laboratory to ordinary people

In 1961, scientists discovered mRNA that can mediate the conversion of genes into proteins.
But until 1990, 29 years later, after a research team injected mRNA directly into skeletal muscle, a protein compiled from this mRNA was found in the tissue, and this protein was not available in skeletal muscle.
In other words, we can use mRNA as a small program to allow cells to produce the proteins we need.
In 1993, scientists were surprised to find that mice injected with influenza virus mRNA showed an immune response.
This means that we can use the pathogen's mRNA as a vaccine to easily produce safe antigens in the body instead of traditional attenuated or inactivated pathogens.

In 1998, American scientists Andrew and Craig discovered that RNA not only allows protein expression, but a small RNA called siRNA can prevent protein synthesis in C.
elegans.
Three years later, researchers discovered that this mechanism is also applicable in mammals, which makes siRNA possible as a medical method.
With siRNA gene interference technology, the two scientists shared the 2006 Nobel Prize in Physiology and Medicine.

Also in 1998, the RNA therapy "fomivirsen", which inhibits retinal inflammation, was approved by the U.
S.
Food and Drug Administration (FDA), and for the first time, RNA therapy went from the laboratory to the clinical application.
Since then, more exciting research advances in RNA therapy have been published, including RNAi (RNA activation) technology that inhibits HIV replication in macrophages and inhibits hepatitis C virus replication.
These results have made it possible to cure a once difficult disease.
In addition to rare diseases and viral infections, RNA therapy also has excellent curative effects on common chronic diseases.
For example, siRNA drugs targeting PCSK9 gene can effectively and lastingly reduce low-density lipoprotein cholesterol levels, thereby achieving the purpose of treating or even preventing hyperlipidemia.
.

Therapies based on RNA technology have sprung up like bamboo shoots after a rain in the 21st century.
In August 2018, Alnylam's Onpattro was approved by the FDA and became the first RNAi therapeutic drug to be marketed.
Moderna and Abbio's new crown vaccines based on mRNA immune technology have also achieved good clinical trial results.
The RNA therapy products of Zhongmei Ruikang and Ruibo Biology are also getting closer and closer to clinical applications.
Compared with traditional drugs, RNA therapy lasts longer after administration, has better specificity and stability, and the price is more acceptable.
More importantly, RNA, as a new and innovative drug, marks A new pharmaceutical revolution is coming.
We can foresee that in the near future, RNA therapy will change from an unfamiliar term to a common treatment plan.
Hillhouse hopes that through investment in RNA therapy, RNA drugs of different types and used in various disease fields will enter the clinic as soon as possible, benefiting the majority of patients.