A groundbreaking study conducted by researchers at the University of Toronto’s Leslie Dan Faculty of Pharmacy has uncovered an ionizable lipid nanoparticle, named iso-A11B5C1, designed for mRNA delivery to muscles while avoiding unintended translation in other tissues.
Led by Assistant Professor Bowen Li, the study, published in Proceedings of the National Academy of Sciences, not only demonstrates the nanoparticle’s exceptional mRNA delivery efficiency but also reveals its potential application as a melanoma cancer vaccine.
This newly identified lipid nanoparticle, iso-A11B5C1, showcases remarkable mRNA delivery efficiency specifically in muscle tissues, minimizing unintended translation in organs such as the liver and spleen. Unlike conventional LNPs that may cause off-target effects, iso-A11B5C1 offers a breakthrough in precision mRNA delivery.
The study brings forth a groundbreaking revelation – mRNA delivered using iso-A11B5C1 triggers potent cellular-level immune responses. This proof-of-concept suggests a paradigm shift in the development of cancer vaccines, particularly for melanoma.
“The substantial anti-tumor effects observed with iso-A11B5C1 underscore its promise as a viable candidate for cancer vaccine development,” says Jingan Chen, a PhD trainee from the Institute of Biomedical Engineering.
Assistant Professor Bowen Li highlights that the study challenges conventional understandings, suggesting that high transfection efficiency in immune cells may not be the sole path to developing effective mRNA vaccines for cancer. Iso-A11B5C1’s unique immune response opens new possibilities for cancer vaccine candidates, particularly in melanoma models.
The research team identified iso-A11B5C1 using an advanced platform designed to swiftly create chemically diverse lipids. This innovative platform, introduced as part of the study, overcomes challenges in the synthesis of ionizable lipids, providing unparalleled speed and precision in the creation of potential therapies.
By combining three different functional groups rapidly, hundreds to thousands of chemically diverse ionizable lipids can be synthesized within an impressive 12-hour timeframe.
“This new platform provides new insights that could help guide lipid design and evaluation processes going forward and allows the field to tackle challenges in RNA delivery with a new level of speed, precision, and insight,” says Yue Xu, a postdoctoral researcher associated with PRiME, a U of T institutional strategic initiative.
The discovery of iso-A11B5C1 not only propels the field of mRNA-based therapies forward but also opens avenues for the development of safer and more effective cancer vaccines. The study’s findings lay the foundation for a new era in targeted mRNA delivery, offering hope for advanced treatments and potential breakthroughs in cancer immunotherapy.
