Researchers have been studying the use of mRNA in disease treatment with great interest since the start of the Covid-19 vaccination campaign in late 2020. Now, scientists are even more intrigued by this technology. Clinical trials for dozens of mRNA-based vaccines, including those for influenza and herpes, are currently underway. Researchers hope that mRNA can be used not only for disease prevention but also for treatment, with one of the key goals being to combat cancer.
However, one of the main obstacles is delivering the mRNA molecule to the right place in the body. Lipid nanoparticles, also known as lipid-based vesicles, can transport RNA into cells, but they are unable to deliver it to specific locations. Jacob Becraft, co-founder and CEO of Strand Therapeutics in Boston, says that this is a problem when it comes to cancer treatment because many anti-cancer therapies “can be extremely toxic to tissues outside the target”.
However, Strand may have found a solution to this problem. They have developed the ability to “program” mRNA similar to computer code, allowing it to perform specific functions – for example, to activate only in certain types of cells, at specific times, and in specific amounts. The company has announced that the US Food and Drug Administration (FDA) has approved clinical trials to test this approach in oncology patients with malignant tumors. Strand plans to start recruiting patients in the spring.
Naturally occurring in all human cells, mRNA carries the genetic plans for producing the proteins that the body needs to function. Synthetic versions used in the Pfizer and Moderna Covid-19 vaccines contain instructions for producing a similar spike protein of the coronavirus. Immune cells in the shoulder muscle recognize the spike protein as foreign and alert the body. The immune system starts to respond and produces protective antibodies. As a result, when the body encounters the spike protein in the actual Covid virus, it is ready to fight.
Using mRNA for cancer treatment works in a similar way. Cancer cells consistently evade the immune system, going unnoticed. However, synthetic mRNA can direct cancer cells to produce specific proteins that inform the immune system about the presence of a tumor.
By utilizing mRNA, Strand sends a message to cancer cells to produce an inflammatory protein called interleukin-12 (IL-12). This, in turn, mobilizes immune cells that destroy cancer cells when they detect the presence of this protein. “Our mRNA penetrates the tumor and causes the tumor to secrete this protein,” says Jacob Becraft. “The tumor becomes a factory.”
In the past, IL-12 has been considered as a potential anti-cancer therapy, but clinical trials in the 1990s were halted due to toxic side effects in patients. At that time, the protein was directly administered into the bloodstream, causing a strong inflammatory response throughout the body. Several companies have attempted to develop safer versions of IL-12, but major pharmaceutical manufacturers seem to have lost interest in this drug. Last year, Bristol Myers Squibb discontinued production, and AstraZeneca and its partner Moderna followed suit.
To keep IL-12 within tumors, Strand scientists have designed a genetic code sequence that instructs the appropriate mRNA to produce the inflammatory protein only when the tumor environment is detected. This sequence is designed to respond to the level of microRNAs, molecules that naturally regulate gene expression and exhibit different signatures in cancer cells compared to healthy cells. When mRNA ends up in a different location than planned, the genetic sequence instructs it to self-destruct.
“We have developed mRNA in a way that they switch off if they reach a place where we don’t want them to reach,” says Jacob Becraft.
Initially, Strand is focusing on easily accessible tumors such as melanoma and breast cancer to demonstrate the effectiveness and safety of their approach. As part of this study, doctors will inject mRNA directly into the tumors and observe the localized effect of the therapy. In the future, Strand plans to administer programmed mRNA throughout the entire body to treat tumors in more distant locations. This way, the therapy would selectively activate in chosen cells and tissues.
Philip Santangelo, a scientist conducting mRNA research at the Winship Cancer Institute of Emory University, believes that Strand’s programming approach has its advantages even if the drug is injected into the tumor site. “If the drug escapes the tumor after administration, its actions will likely be limited to the tumor itself,” says Santangelo.
IL-12 can be identified in the blood, so researchers will be able to perform blood tests and check for the presence of the protein. Strand also plans to monitor various organs to see where the protein ends up. If the therapy works as intended, the protein should not be found outside the tumor.
Just like computer circuits, genetic circuits can sometimes make mistakes, says Ron Weiss, a professor of biological engineering at MIT, who co-founded Strand and now serves as an advisor. “If your genetic circuit makes a mistake one out of ten times, it’s not worth using it as a therapy,” Weiss says. “If it does it one out of a million times, then that’s pretty good.”
Strand’s research and other early attempts with this type of genetic circuit will help assess how well they work. “The idea is that genetic circuits can really have a significant impact on safety and effectiveness,” Weiss says.
Weiss was a pioneer of genetic circuit ideas, with the first ones being based on DNA. When Becraft began his doctoral studies in 2013, he joined Weiss’ lab to work on genetic circuits for mRNA. At that time, many scientists doubted the potential of mRNA.
Now, Weiss envisions the possibility of programming increasingly complex actions using genetic circuits to create precise therapies. “This opens doors for developing therapies that match the complexity of biology.”
FAQ:
1. What is mRNA?
mRNA (messenger RNA) is a ribonucleic acid molecule that carries genetic instructions to cells for the production of proteins needed for the functioning of the body.
2. What research is currently being conducted regarding the use of mRNA?
Currently, clinical trials are underway for dozens of mRNA-based vaccines, including those for influenza and herpes. Additionally, researchers are studying the use of mRNA in cancer treatment.
3. What are the main obstacles to using mRNA for cancer treatment?
One of the main obstacles is delivering the mRNA molecule to the right place in the body. The lipid nanoparticles used so far can transport mRNA into cells, but they are unable to deliver it to specific locations.
4. How does Strand Therapeutics plan to solve this problem?
Strand Therapeutics has developed the ability to “program” mRNA to perform specific functions only in certain types of cells, at specific times, and in specific amounts. This allows for the direct delivery of mRNA into tumor cells and the production of the necessary inflammatory protein only in the presence of a tumor.
5. How does using mRNA for cancer treatment work?
Synthetic mRNA directs cancer cells to produce specific proteins that inform the immune system about the presence of a tumor. This mobilizes immune cells to destroy cancer cells when they detect the presence of these proteins.
The source of the article is from the blog lokale-komercyjne.pl