Make a penetration of small chemistry only more secure, stronger and smarter vaccines

In a new paper in The nature of biomedical engineeringResearchers at the University of Pennsylvania explain that adjusting the ionized fat structure, which is a major component in the lipoplasty (LNPs) that provide flexible, not only reduces inflammation, but also reduces the effectiveness of the vaccine to prevent or treat a group of diseases, from Covid-19 to cancer.

The main change? Add phenol groups and chemical compounds with anti -inflammatory properties famous in foods such as olive oil. Michael C. Mitchell, Assistant Professor in Biological Engineering (Be) and the largest newspaper: “By mainly changing the recipe for these fats, we were able to make them work better with lower side effects.” “It is a victory.”

Recipe review

Until now, ionized fats have been manufactured in LNPS – one of four types of fats in LNPS, and it can be said that they are the most important – to a large extent using chemical reactions that combine two components in a new molecule, very similar to two midwives of sandwich.

“Since these operations were very successful, there was not much effort to search for alternatives,” says Ninqiang Gong, a former post -PhD fellow at Mitchell Lab and co -author of the newspaper.

If we look back in the history of chemistry, the team finds an alternative approach: Manish’s reaction, named after the German chemist that he discovered more than a century ago.

Instead of two elements, the mannich reaction combines three sects, allowing a larger range of molecular results. “We were able to create hundreds of new fats,” says Gong.

Explore that the fat library prompted the team to discover that adding the phenol group – a mixture of hydrogen and oxygen connected to a loop of carbon molecules – greatly reduced inflammation.

“It is like a secret sauce,” says Gong. “The phenol group not only reduces the side effects associated with LNPS, but it improves its effectiveness.”

Phenols

Previous studies have found that phenol -containing compounds reduce inflammation by canceling the harmful effects of free radicals, and non -restricted electrons that can disrupt body chemistry.

Many free radicals and a very few antioxidants lead to “oxidized stress”, which lands from proteins, destroys genetic substances and can even kill cells.

By checking various signs related to oxidative stress, researchers compared the inflammatory effects of LNPs made using different fats.

“The best LNP is the best performance, which we created using phenol -containing fats that result from the Mannich’s reaction, already caused less inflammation.”

Less inflammation, higher performance

With these encouraging signs of low inflammation, the researchers tested whether the new fats improve the performance of the vaccine.

Through multiple experiments, C-A16 LNPs, which included the most anti-inflammatory fat, surpasses LNPs used in Marna technologies during the market.

“Reducing oxidative stress makes it easy for LNPs to do their job,” says Dongyoon Kim, a post -PhD fellow at the Mitchell Laboratory and co -author of the paper.

The C-A16 LNPs has not only produced longer effects, but also improving the effectiveness of genetic liberalization tools such as CRISPR and vaccine power to treat cancer.

Control genetic diseases, cancer and Covid-19

To test the new C-A16 fat in an animal model, researchers used it for the first time to present it in the gene cells that makes Fireflies Glow- a classic experience to verify the strength of genetic instructions.

The glow in the mice was brighter about 15 times more compared to the LNPs used in the onpattro, a certified treatment from the Food and Drug Administration (FDA) of the HATTR, which is a rare genetic disease.

The C-A16 fats also helped genes editing tools such as Krisper to do better work in repairing the defective gene that causes a hat. In fact, they have died more than the effectiveness of treatment in the mouse model compared to the current delivery methods.

In cancer treatments, the results were striking. In an animal model of skin cancer, a decrease in flexible cancer treatment is delivered with C-A16 fats more effective tumors than the same treatment that was delivered with LNPs used in Covid-19 vaccines. The new fats also gave T-cells to combat cancer, which helps them to identify cancer cells and destroy them more efficiently-with less oxidizing pressure.

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

“By causing lower interruption of cellular machines, new fat containing phenol can enhance a wide range of LNP applications,” says Kim.

Old chemistry, new borders

In addition to investigating the immediate capabilities of the new fat to reduce side effects in flexible vaccines, researchers are looking to explore how to ignore chemical processes such as mannich’s interaction from describing new enhanced recipes LNP.

“We tried to apply one reaction that was discovered a century ago, and we found that it could greatly improve the advanced medical treatments,” Mitchell says. “It is interesting to imagine what is still to be discovered.”

This study was conducted at the Faculty of Engineering and Applied Sciences at the University of Pennnering and the College of Medicine in Penn Medicine, and supported by the National Innovator’s National Institutes of National Institutes (NIH), which is the Burroughs Wellcome Cannerial Professional (NIH) (NIH) (NIH) (CBET-215491), Association American Cancer (RSG-2222-01-ET), two colleagues of the graduate research research of American National Sciences (DGE 1845298, DGE 1845298), GEM Fellowship, and NIH/National Cancer Pre-Doc (F9984294).

Additional authors from the authors from Rohan Balinki, Qiangkish Shi, Xuexiang Han, Lulu Xue, Junchao Xu and Christian G. Figueroa-hepada from Penn Engineering; Drew Weissman, Mohamed Gabriel his pain, Rakan Al -Mita and Jarima Duvidi from Pennsylvania Medicine; Zilin Ming, Tianyu Luo and Jinghong Li from USTC.