The absorption process of some modern vaccines, which use the messenger RNA (mRNA) technique, is not simple.
Some nucleic acids can be extremely sensitive to degradation, particularly in the digestion process.
Thinking about how not to lose these substances, researchers at the Massachusetts Institute of Technology (MIT) have developed a way to deliver the RNA to the body through a pill – which would prevent the loss of material and would be better received by those who fear vaccines.
The results of the experiment were published in the scientific journal Cell.
As these nucleic acids are susceptible to attenuation when they enter the body, they need to be transported by protective particles.
The research team, led by Giovanni Traverso, an MIT professor and gastroenterologist at Brigham and Women’s Hospital, and Robert Langer, also of MIT, used a different type of polymeric nanoparticle — macromolecules formed from smaller structural units to generate this ‘ protection’ to RNA.
The polymer, called poly(beta-amino esters), is the material used to form the particles that efficiently deliver RNA to the body.
clinical trials
The research was initially carried out with mice. To test the effectiveness of the particles, the scientists injected the substance into the animals’ stomachs, without using the capsule developed in the laboratory.
The results showed that the nucleic acid absorbed by the organ encodes a specific protein, called a reporter, that can be detected in the tissue if the cells successfully absorb the mRNA.
In the course of the studies, the researchers found the reporter protein in the stomachs of the mice and also in the liver — something that suggests that the RNA had been taken up in other organs of the body and then transported to the liver, which filters the blood and eliminates toxins.
In a second step, testing pigs, the scientists dehydrated elements of the RNA nanoparticles and placed them in their capsules – like those traditional pill coatings.
The team managed to put about 50 micrograms of mRNA per capsule, and ingesting three capsules, into the pigs’ stomachs, totaling 150 micrograms of mRNA. To give you an idea of comparison, Covid-19 vaccines have between 30 and 100 micrograms of mRNA.
“What this allows us to do now is to reduce the total amount of nanoparticles that we are administering,” Ameya Kirtane, a researcher at MIT, said in a statement.
The reporter protein was successfully produced by the stomach cells of pigs. However, the researchers did not find it anywhere else on the body — such as in mice.
different approaches
In previous research by the team, the group demonstrated that branched versions (branches attached to the main chain) of the polymers are more effective than linear polymers (composed of many long strands joined together, as if they were a continuous rope) in protecting nucleic acids and their entry into cells.
In 2019, researchers designed a capsule that, once ingested, delivered solid medications, such as insulin, to the digestive tract.
In the 2021 survey, the team took a different approach and used an even bigger pill to deliver monoclonal antibodies in liquid form. And with the success of the responses, they decided to try the drug to deliver nucleic acids, which are also large molecules.
With the results, the scientists also found that using two of these polymers together is more effective than just one.
Traverso said in a statement that successfully delivering RNA to the intestinal tract opens up several approaches to therapy, including potential oral vaccination.
Alex Abramson of the MIT team said the researchers hope to increase RNA uptake in other organs by changing the composition of nanoparticles or giving larger doses. “However, it may also be possible to generate a strong immune response with delivery only to the stomach,” he points out.
He believes that the results serve not only to provide an alternative to vaccines, but also to treat diseases that affect the stomach and intestine.
“When you have systemic delivery via intravenous injection or subcutaneous injection, it is not very easy to reach the stomach. […] We see the results as a potential way to treat different diseases that are present in the gastrointestinal tract.”
Source: CNN Brasil
