As millions of people already know, the most common side effects of mRNA vaccines such as Kovid -19 shots are inflammation: agony, redness and unhealthy of one or two days. But what if MRNA vaccines can be re -designed to completely sideline that response?

In a new paper in Nature biomedical engineeringResearchers at the University of Pennsylvania suggest that a major component of lipid nanops Swelling But from Covid -19 to cancer, also promotes vaccine effectiveness for preventing many diseases or treatment.

Main change? Phenol groups Anti -inflammatory Famous properties in foods like olive oil.

By changing the recipe for these lipids, we were able to do them better with less side effects. This is a win. ,

Michael J. Michelle, Associate Professor and Senior Writer of Paper in Michelle, Bio -Engineering (BE)

Recipe

So far, INigable Lipids in LNP – one of the four types of lipids in LNP, and of course the most important – has been synthesized using large -scale chemical reactions that combine two components into a new molecule, much like two parts coming together of a sandwich.

“Because these procedures have been so successful, a former postdorl fellow and the co-first writer of the paper at Mitchell Lab,” not much effort has been made to find options. ”

Given the history of chemistry, the team found an alternative approach: Mannich Reaction, named after the German chemist, who discovered it more than a century ago.

Instead of two components, the vantage reaction combines three precursors, which allows for a large variety of molecular consequences. “We were able to create hundreds of new lipids,” Gong says.

The “library” of the lipids to find out the team to find a phenol group – a combination of hydrogen and oxygen attached to a ring of carbon molecules – significantly low inflammation.

“It is like secret chutney,” Gong says. “Phenol group not only reduces the side effects associated with LNP, but also improves their efficacy.”

Power of phenols

Previous studies have found that phenol -containing compounds reduce inflammation by denying the harmful effects of free radicals, which can disrupt the body’s chemistry to molecules with unpublished electrons.

Lots of free radicals and very low antioxidants result in “oxidative stress”, which lowers proteins, damage genetic material and can also kill cells.

By examining various markers associated with oxidative stress, researchers compared the inflammatory effects of LNP using various lipids.

“The best performing LNP, which we made using a phenol-containing ianeezable lipids produced by the vow reactions, caused a really low swelling,” Emily Han, a doctoral student in BE and the co-writer of the paper called Emily Han.

Low swelling, high performance

With these encouraging signs of low inflammation, researchers conducted the next test whether the new lipids have also improved the vaccine performance.

Crossing several experiments, C-A16 LNPs, which included the most anti-inflammatory lipids, improves LNPs used in on-the-market MRNA technologies.

“It becomes easy for LNP to reduce oxidative stress in the postdorel fello and paper co-first writer Dongian Kim in Mitchell Lab.

C-A16 LNPS not only produced long-lasting effects, but also improved Efficacy of CRISPR and vaccine power to treat cancer such as gene-editing tools.

Genetic Disease, Cancer and Fighting Covid -19

To test how well the new C -A16 lipid worked in an animal model, researchers first used them to give them cells that make the genes shiny – a classic experiment to check the strength of genetic instructions.

The brightness in mice was about 15 times brighter than the LNP used in Onpattro, a rare genetic liver disease was a FDA-approved treatment for hereditary transthiratin amylidosis (hattr).

The C-A16 lipid also helped in gene-editing tools such as crispr, which does a better job that cures defective genes that cause hattr. In fact, they doubled the effectiveness of treatment in a mouse model compared to current distribution methods.

In the treatment of cancer, the results were equally striking. In an animal model of melanoma, a mRNA cancer treatment with C-A16 lipids, which is three times more effectively more effectively than the same treatment given with LNPs used in covid-19 vaccines. The new lipids also promoted cancer -fighting T cells, helping them to identify and destroy tumor cells more efficiently – and with low oxidative stress.

Finally, when the team used the C-A16 lipids to prepare the Covid-19 MRNA vaccines, the immune response in the animal model was five times stronger than the standard fears.

“By creating low disruption in cellular machinery, new, phenol -containing lipids can increase a wide range of LNP applications,” says Kim.

Old Chemistry, New Front

In addition to checking the immediate ability of new lipids to reduce side effects in MRNA vaccines, researchers are ready to find out how to ignore chemical procedures such as the vow reactions, unlocking new LNP-growing dishes.

Says Michelle, “We tried to implement a reaction a century ago, and found that it could significantly improve state -of -the -art medical remedies.” “It is exciting to imagine what else is yet to be discovered.”