Chemical modification of mRNA for enhancing RNA therapeutics

"Messenger RNA (mRNA) therapies, such as some COVID-19 vaccines, have shown promise for treating many diseases. But today's mRNA medicines still face real challenges. They can break down quickly in the body, sometimes trigger unwanted immune reactions, and may start working in places where they shouldn't. All of this limits how effective and safe they can be. My research focuses on creating a new kind of mRNA that is safer, more stable, and only turns "on" when it reaches the right cells. To make this possible, I plan to add small, removable chemical "locks" to the mRNA. These keep mRNA turned off during delivery so it doesn't produce proteins at the wrong time. Once the mRNA encounters specific natural molecules inside target tissues, the locks are removed and the mRNA becomes active. This project also takes advantage of both major types of mRNA. Linear mRNA can be fragile but good at producing proteins, and circular mRNA that lasts longer in the body and is less likely to activate an immune response. I will combine the strengths of both by temporarily turning linear mRNA into a circular form using reversible chemical links. In this temporary circular form, the mRNA stays protected and inactive. When the chemical lock is opened, the mRNA returns to its normal shape and begins working as intended. This research has three goals: 1. Create the chemical "locks" that control when the mRNA becomes active; 2. Test how these locks affect the stability and performance of the mRNA; and 3. Explore how the technology can be used in different biological systems. This work could lead to new, safer, and more precise mRNA-based treatments"