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Biomedical engineering

Redesigned mRNA Vaccines Show Promise in Reducing Side Effects and Boosting Effectiveness

Strategic Insights

— 2 min read

Researchers at the University of Pennsylvania have developed a new approach to designing mRNA vaccines that could potentially reduce side effects and improve their effectiveness in preventing or treating a range of diseases, from COVID-19 to cancer. By tweaking the structure of the ionizable lipid, a key component of the lipid nanoparticles (LNPs) that deliver mRNA, the team was able to create a new lipid that substantially reduced inflammation and improved vaccine performance.

Key Takeaways:

  • The researchers developed a new approach to designing mRNA vaccines by revising the recipe for the ionizable lipid, a key component of the lipid nanoparticles (LNPs) that deliver mRNA. They used the Mannich reaction, a chemical process discovered over a century ago, to create a new lipid that added phenol groups, which have anti-inflammatory properties.
  • The new lipid, C-a16, substantially reduced inflammation and improved vaccine performance in multiple experiments. It outperformed LNPs used in on-the-market mRNA technologies and improved the efficacy of gene-editing tools like CRISPR and the potency of vaccines for treating cancer.
  • The C-a16 lipids were tested in animal models and showed promising results in treating genetic disease, cancer, and COVID-19. They helped gene-editing tools like CRISPR fix the faulty gene that causes hereditary transthyretin amyloidosis (hATTR), a rare genetic liver disease, more effectively than current delivery methods.
  • In cancer treatments, the C-a16 lipids shrank tumors three times more effectively than the same treatment delivered with the LNPs used in the COVID-19 vaccines. They also gave cancer-fighting T cells a boost, helping them recognize and destroy tumor cells more efficiently - and with less oxidative stress.
  • The new lipids also gave a stronger immune response in animal models for COVID-19 mRNA vaccines, with effects five times stronger than with standard formulations.

Statistics:

  • 15 times brighter glow in mice compared to the LNPs used in Onpattro, an FDA-approved treatment for hereditary transthyretin amyloidosis (hATTR)
  • 3 times more effective tumor shrinkage in an animal model of melanoma compared to the same treatment delivered with the LNPs used in the COVID-19 vaccines
  • 5 times stronger immune response in animal models for COVID-19 mRNA vaccines compared to standard formulations
  • 100s of new lipids created using the Mannich reaction

Sources:

  • University of Pennsylvania School of Engineering and Applied Science (Penn Engineering)
  • Perelman School of Medicine (Penn Medicine)
  • U.S. National Institutes of Health (NIH)
  • U.S. National Science Foundation (NSF)
  • American Cancer Society (ACS)
  • GEM Fellowship
  • NIH/National Cancer Institute Pre-doc to Post-doc Transition Award (F99 CA284294)

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